Podcasts about CRS

In the first episode of our "AI in Real Estate" series, Patricia Orange, CRS, joins us to explore how real estate professionals can use artificial intelligence to elevate their business without losing the personal touch that builds trust. From ChatGPT to marketing automation, Orange shares how she blends innovation with authenticity—and why staying educated and adaptable remains key in an evolving market.

This Day in Legal History: Nevada Admitted as 36th StateOn October 31, 1864, Nevada was officially admitted as the 36th state of the United States, a move driven as much by wartime politics as by the territory's readiness for statehood. With President Abraham Lincoln seeking re-election and needing support for the proposed 13th Amendment to abolish slavery, the Republican-controlled Congress saw strategic value in adding another loyal Union state. Although Nevada's population was below the threshold typically required for statehood, its vast mineral wealth and political alignment with the Union helped accelerate the process. To meet the tight timeline ahead of the 1864 election, Nevada's leaders moved quickly to draft a state constitution.Facing logistical challenges in sending the document from Carson City to Washington, D.C., Nevada officials made the unprecedented decision to transmit the entire text—over 16,000 words—via telegraph. The transmission took over 12 hours and cost more than $4,000, making it the longest and most expensive telegram ever sent at the time. The decision proved effective: the telegram reached the capital in time, and Congress formally approved Nevada's admission on the same day.The speed and cost of Nevada's telegraphic constitution became a symbol of the urgency and improvisation of Civil War-era governance. The state's motto, “Battle Born,” reflects both its literal birth during the Civil War and the political battle over slavery and Union preservation. Nevada's admission also helped secure support for Lincoln's re-election and for the 13th Amendment, which passed Congress in January 1865.In a recently disclosed legal filing, Immigration and Customs Enforcement (ICE) sought taxpayer information on over 1.28 million individuals from the IRS, though only about 47,000 records matched. The request, part of a broader effort to access data on individuals under final removal orders, was submitted under a carve-out in Section 6103 of the Internal Revenue Code, which permits limited disclosures during criminal investigations. The IRS initially rejected ICE's requests citing legal constraints, but a memorandum of understanding in April allowed for limited data sharing. A subsequent refined request from ICE in June targeted a smaller group of 1.27 million, but again, only a small percentage matched IRS records, and many failed to meet legal standards for processing.The case arose from a lawsuit filed by taxpayer advocacy groups and unions, which argue that these disclosures violate the Tax Reform Act, the Privacy Act, and the Administrative Procedure Act. Plaintiffs are seeking a preliminary injunction to halt further sharing. Internal emails reveal IRS officials were concerned about the unprecedented scale and legality of the request, and officials emphasized the need to keep the data sharing confidential. The IRS typically handles about 30,000 such data requests a year, each requiring detailed justification and high-level agency approval. Critics warn that this massive data handover poses urgent threats to taxpayer privacy and due process rights.ICE Sought Records on 1.3 Million Taxpayers, Filing Shows (1)U.S. District Judge Carl Nichols praised two federal prosecutors, Samuel White and Carlos Valdivia, for their handling of a case against Taylor Taranto, despite both being suspended by the Justice Department the day before. The suspension followed their reference to January 6 rioters as “a mob of rioters” and mention of Donald Trump allegedly sharing Barack Obama's address in a sentencing memo. Judge Nichols commended their work as professional and exemplary, stating they upheld the highest prosecutorial standards.Taranto was sentenced to 21 months in prison for firearm and hoax-related charges after being arrested near Obama's D.C. residence in 2023. However, he will not serve additional time due to pretrial detention. Though originally charged for participating in the Capitol riot, those charges were dropped under President Trump's mass clemency order for January 6 defendants issued at the start of his second term. Taranto's defense claimed his statements about explosives were meant as “dark humor” and that he hadn't committed any violence.After White and Valdivia's suspension, a revised sentencing memo—stripped of January 6 and Trump references—was filed by two replacement prosecutors, including a senior DOJ official. The incident reflects broader tensions under the Trump administration, which has repeatedly moved to minimize references to Capitol riot violence and penalize prosecutors involved in politically sensitive cases.US judge praises prosecutors who were suspended after referring to January 6 ‘mob' | ReutersA federal judge allowed the Trump administration to move forward with firing nearly all remaining employees of the Department of Justice's Community Relations Service (CRS), an agency established in the 1960s to mediate racial and ethnic conflicts. U.S. District Judge Indira Talwani, while denying a temporary restraining order sought by civil rights groups, noted that the plaintiffs failed to show immediate, irreparable harm. However, she also stated that the groups are likely to succeed in proving that the executive branch cannot lawfully dissolve a congressionally created agency.The lawsuit, brought by 11 organizations including the NAACP and the Ethical Society of Police, challenges the Justice Department's recent “reduction in force” that would leave just one CRS employee. The move follows a pattern under the Trump administration, which has rejected all new requests for CRS services and proposed no funding for the agency in its budget. Plaintiffs argue that a termination notice stating the layoffs aim to “effectuate the dissolution” of CRS confirms unlawful intent.Although Talwani's ruling allows the firings to proceed, she emphasized that the final outcome may favor the plaintiffs as the case continues. The layoffs coincide with a government shutdown that began October 1, meaning the employees would have been furloughed regardless. The DOJ claims it is merely reorganizing, not eliminating, the agency, though it concedes that only Congress has the authority to formally abolish it.Judge allows Trump administration to fire most of DOJ race-relations agency's employees | ReutersHagens Berman Sobol Shapiro, a prominent plaintiffs' law firm, is under scrutiny in two high-profile class actions, facing judicial criticism and potential sanctions. In Seattle, a federal judge sanctioned the firm for over $223,000 after finding it misled the court and opposing counsel about its client's withdrawal from an antitrust case against Apple and Amazon. The judge said Hagens Berman failed to disclose that their client, who later disappeared from proceedings, had expressed his intent to exit the case months earlier. The firm argues it acted ethically under client confidentiality rules and has asked the judge to revise her dismissal ruling.In a separate matter in Philadelphia, the firm faces possible new sanctions in long-running litigation over thalidomide-related birth defect claims. A special master found misconduct, including altering an expert report and advancing claims lacking legal merit. While Hagens Berman disputes the findings, calling them outside the master's authority and biased, U.S. District Judge Paul Diamond upheld the report. The firm has now requested that Diamond recuse himself, citing an appearance of bias due to his close coordination with the special master.In both cases, Hagens Berman maintains its actions were in good faith and within legal and ethical bounds, while critics and courts point to patterns of misrepresentation and overreach.Law firm Hagens Berman battles sanctions in Apple, thalidomide cases | ReutersThis week's closing theme is by Camille Saint-Saëns.Camille Saint-Saëns was a French composer, organist, conductor, and pianist whose long career spanned the Romantic era and touched the early 20th century. Born in Paris in 1835, he was a child prodigy who began composing at the age of three and gave his first public performance at ten. Saint-Saëns was celebrated for his extraordinary versatility, writing symphonies, concertos, operas, chamber music, and choral works. Though deeply rooted in classical forms, he was an early supporter of contemporary composers like Liszt and Wagner, even as he remained skeptical of more radical modernism. His music often combined technical brilliance with elegance, and his clear, structured style made him a bridge between tradition and innovation. He was also a prolific writer and amateur astronomer, and his intellectual breadth sometimes earned him criticism from those who found his music too refined or academic. Still, Saint-Saëns maintained influence across Europe, and his works remain staples of the concert repertoire.This week's closing theme is Saint-Saëns' Danse Macabre. Originally a song for voice and piano based on a poem by Henri Cazalis, Saint-Saëns later reworked Danse Macabre into a tone poem for orchestra. It depicts Death summoning the dead from their graves at midnight on Halloween for a wild, skeletal waltz. A solo violin—tuned unconventionally to evoke a harsh, eerie sound—plays Death's dance theme, while xylophone rattles mimic clacking bones. The piece was controversial at its premiere in 1875 but quickly became a concert favorite, especially around Halloween. With its vivid orchestration and playful macabre imagery, Danse Macabre is one of classical music's most iconic musical depictions of the supernatural, perfectly capturing the spirit of the season.Without further ado, Saint-Saëns Danse Macabre—enjoy! This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.minimumcomp.com/subscribe

Stephen Barnes, program architect of Sierra Leone's GO-FOR-GOLD residency initiative, reveals how 4,000 families will secure citizenship in 90 days – without traditional CBI legislation. Africa's fastest-growing economy chose special naturalization over citizenship by investment: What does this mean for the industry's future? Watch to discover the program parameters and why this non-CRS jurisdiction is attracting investors.Learn more about the Sierra Leone GO-FOR-GOLD program here.

Senator Ron Johnson (R-WI) joined The Guy Benson Show today to discuss the ongoing government shutdown and why Democrats are holding it hostage to score political points. Sen. Johnson criticized the nonsensical shutdown as programs like SNAP hang in the balance and hungry Americans face the fallout. Johnson explained that Republicans remain open to negotiating on health care, but Democrats continue doubling down on subsidies instead of passing a clean CR and continue negotiations. Relatedly, Sen. Johnson shared details about his new bill aimed at permanently ending government shutdowns by passing clean CRs every two weeks instead of having the government grind to a halt. Finally, Sen. Johnson weighed in on the explosive "Arctic Frost" investigation, and you can listen to the full interview below! Learn more about your ad choices. Visit podcastchoices.com/adchoices

Viele aus unserer Community wollten wissen: Wie sicher ist mein Geld im Ausland wirklich? In dieser Folge gehe ich auf exakt 13 eurer Fragen ein – ehrlich, praxisnah und mit Beispielen aus der Realität. Was dich erwartet: • Länder, die derzeit als besonders sicher gelten? • häufige Fehler, die Anleger beim Thema Auslandskonto machen! • was du über Einlagensicherung und „Bail-in“ wirklich wissen musst! • und warum es sehr riskant ist, nur 1-2 Inlandskonten zu haben? Die Antworten könnten dich überraschen – vor allem, wenn du glaubst, dein Geld wäre auf der Bank automatisch sicher.

Este episodio es patrocinado por HalloCasa, la tarjeta de presentación digital optimizada para SEO dirigida a agentes inmobiliarios. ¿Buscas al agente adecuado sin importar dónde estés?Descubre y conecta con los mejores agentes inmobiliarios del mundo: https://home.hallocasa.com/En este episodio de HalloCasa conversamos con Alejandro Escudero, Director de Estrategia Global de la National Association of REALTORS® (NAR), la asociación inmobiliaria más grande de Estados Unidos, con presencia en más de 75 países.Hablamos sobre la misión de NAR, su presencia en América Latina, los beneficios para los miembros internacionales, cómo afiliarse desde Latinoamérica, y las certificaciones internacionales como CIPS y CRS que ayudan a elevar la carrera de cualquier agente inmobiliario.También exploramos NAR en Español, una plataforma creada para facilitar el acceso a recursos, formación y herramientas a profesionales hispanohablantes, y cerramos con consejos prácticos para quienes desean iniciar una carrera inmobiliaria.Temas destacados:00:01:00 Introducción00:04:00 Países donde opera NAR en Latinoamérica00:05:00 La misión de NAR00:11:00 Beneficios para miembros00:14:00 Cómo afiliarse desde Latinoamérica00:18:30 Certificaciones internacionales (CIPS, CRS y más)00:22:00 NAR Español: Recursos en línea00:33:00 Consejos para nuevos agentes00:36:00 Conclusión y contactoMira el episodio completo y descubre cómo llevar tu carrera inmobiliaria al siguiente nivel con NAR.Datos de Contacto:  / alejandroescuderorodriguez  https://www.nar.realtor/alejandro-esc...aescudero@nar.realtor

C'était il y a 20 ans à Clichy-sous-Bois en banlieue parisienne. Le 27 octobre 2005, Zyed Benna, 17 ans, et Bouna Traoré, 15 ans, mouraient électrocutés après avoir été pourchassés par la police. Les adolescents s'étaient réfugiés dans un transformateur EDF pour tenter d'échapper à un contrôle d'identité. Le drame avait déclenché 21 nuits d'affrontements entre jeunes et forces de l'ordre en banlieue parisienne d'abord, puis partout en France. Des révoltes qui ont permis aux habitants de ces quartiers populaires de montrer les discriminations qu'ils vivaient au quotidien, sur le plan social, mais aussi géographique. 20 ans plus tard, RFI est retourné à Clichy-sous-Bois. Si les infrastructures de la ville se développent (le métro y fera d'ailleurs son arrivée en 2027), le poids de l'histoire tragique de Zyed et Bouna pèse toujours sur les Clichois. Depuis 2019, c'est un peu plus facile d'aller et venir à Clichy-sous-Bois, même si, à 15 kilomètres seulement de Paris, la ville reste mal desservie par les transports en commun. C'est ici que Mehdi Bigaderne a grandi. Il avait 23 ans en 2005 : « J'étais à l'université de Saint-Denis, je mettais trois heures, alors peut-être qu'on met un peu moins, je ne sais pas, aujourd'hui, mais on met quand même beaucoup de temps et, effectivement, on ne part pas de la même ligne de départ, ça, c'est certain. Et cette question des discriminations, elle n'est pas vraiment prise au sérieux. » Ce tramway, le T4, avait pourtant été annoncé en personne par le président Jacques Chirac dès 2006, au lendemain des violences urbaines, nées ici, dans un quartier fragile, mais tranquille, qui s'est brutalement retrouvé sous le feu des projecteurs : « Je m'en souviens comme si c'était hier, parce que c'est tellement marquant. Je suis un enfant de la ville et c'est la première fois que je voyais la ville dans cet état-là, avec des brigades de CRS pratiquement dans chaque immeuble. Et puis, après, on a vu arriver un hélicoptère – moi, j'avais l'impression d'être à Bagdad, à un moment donné – qui tournait autour des immeubles avec un projecteur, qui était pénétrant dans les appartements, déjà qu'ils n'étaient pas très grands… » À écouter aussiBanlieues 2005 : retour à Clichy-sous-Bois La mort de Zyed et Bouna a laissé des cicatrices profondes dans le quartier À l'époque, l'ampleur de la réponse sécuritaire choque les habitants qui pleuraient deux enfants du quartier : Zyed Benna, 17 ans, et Bouna Traoré, 15 ans. Ce qui n'arrange rien au rapport fragile entre police et population… Olivier Klein, maire actuel, était adjoint à la jeunesse et à la ville il y a 20 ans : « Quand les maires de l'époque ont vu le président de la République, il a demandé quelles seraient les urgences. Les deux maires, ensemble, ont dit : "Il nous faut un tramway – une des raisons de la popularisation, c'est l'enclavement, le temps pour aller bosser, le temps pour aller étudier, etcetera –, et on a besoin d'avoir un commissariat de plein exercice – pour que la police puisse être comme un poisson dans l'eau dans nos quartiers". » À lire aussiFrance: il y a 20 ans, la mort de Zyed Benna et Bouna Traoré à Clichy-sous-Bois Les discriminations, un enjeu majeur En 2012, un commissariat sort de terre à Clichy. Les cicatrices sont encore bien visibles, mais d'après Mehdi Bigaderne, qui a cofondé l'association ACLEFEU pour faire remonter la parole des quartiers populaires auprès des institutions, constate que les choses changent petit à petit : « Les commissaires qui ont dirigé ce commissariat étaient ouverts à travailler avec les associations, donc on voyait qu'il y avait une volonté de se dire, s'il y a des incidents, on peut s'en parler… En revanche, je pense qu'ils sont limités parce que, je ne crois pas me tromper en disant ça, c'est qu'on a aussi un problème qui est plutôt général. Moi, je suis content de pas avoir revécu un tel drame sur la ville, mais il y en a eu d'autres malheureusement, et il faut que l'État prenne à bras-le-corps ce sujet-là qui, aujourd'hui, peut être un fonds de commerce pour certains politiques. » En 20 ans, les visages enfantins de Zyed et Bouna ont été rejoints par des dizaines de sourires similaires dans les marches blanches. D'après le média Basta!, le nombre de décès annuels imputables aux forces de l'ordre françaises a doublé depuis les années 2000. À lire aussiIl y a dix ans, les banlieues s'embrasaient dans toute la France

This episode is brought to you by HalloCasa, the SEO-ranked digital business card for real estate agents. Looking to find the right agent, no matter where you are?Visit https://home.hallocasa.com to discover and connect with top real estate agents globally.In this episode of HalloCasa, we speak with Alejandro Escudero, Director of Global Strategy at the National Association of REALTORS® (NAR), the largest trade association worldwide with over 1.5 million members.Alejandro shares valuable insights into NAR's international initiatives, the Global Ambassador and Coordinator programs, and the importance of understanding local real estate ecosystems around the world.He also discusses global certifications such as CRS and CIPS, clarifies the difference between real estate brokers and REALTORS®, and highlights emerging trends in global real estate, proptech, and international collaboration.If you're a real estate professional looking to expand globally, understand international standards, or connect with REALTORS® worldwide, this episode is for you.Timestamps:00:01:00 Introduction00:02:00 National Association of REALTORS®00:08:30 Global Ambassadors and Coordinators Program00:09:30 Understanding Local Culture, Legal Systems, and Markets00:13:30 REALTORS® vs Brokers and Professional Standards00:16:30 Global Certifications: CRS and CIPS00:19:30 Real Estate Trends, NAR's REACH Program & Proptech00:23:30 Common Challenges and Misconceptions of Associations00:25:30 Tips to Succeed as a Real Estate Agent00:32:30 Conclusion and Final WordsContact Information:  / alejandroescuderorodriguez  https://www.nar.realtor/alejandro-esc...aescudero@nar.realtor

This episode provides comprehensive coverage of key clinical trial updates from the 2025 International Myeloma Society (IMS) Annual Meeting in Toronto, with special focus on bispecific antibodies and novel immunotherapies across the multiple myeloma disease continuum—from smoldering disease through relapsed/refractory settings. Dr. Alfred Garfall provides expert commentary on study design, efficacy, safety considerations, and clinical implications.Topics Covered1. SMOLDERING MULTIPLE MYELOMALINKER-SMM1Phase 2, open-label study of linvoseltamab monotherapy (200 mg) in patients with high-risk smoldering multiple myeloma by 20/2/20 or PETHEMA criteria, with 2-year treatment duration.Discussion Points:Appropriateness of 2-year treatment duration for precursor conditionEfficacy and MRD-negative ratesSafety considerations in asymptomatic populationPatient selection if available today2. NEWLY DIAGNOSED MULTIPLE MYELOMAMajesTEC-5Phase 2 trial evaluating three teclistamab-daratumumab-based induction regimens in 49 transplant-eligible NDMM patients, followed by auto-transplant and fixed-duration Tec-Dara maintenance.Discussion Points:Post-induction MRD-negativity rates with Tec-DR and Tec-DVRGrade 3-5 infection rates and infection-related deathsQuestionable utility of bortezomib and need for ASCT with 100% MRD-negativityHigh infection prophylaxis requirementsMagnetisMM-6Phase 1/2 dose-finding study of fixed-dose elranatamab 76 mg Q4W with Dara-Len in 37 transplant-ineligible NDMM patients (median age 75 years).Discussion Points:VGPR or better ratesSafety profile including infections and CRS/ICANSRisk of continuous therapy in elderly/frail populationLINKER-MM4Phase 1/2 study of linvoseltamab monotherapy in NDMM with both transplant-eligible and transplant-ineligible pathways, exploring three dose levels (50, 100, 200 mg).Discussion Points:Efficacy of single-agent Linvo in NDMMWhether any NDMM population could achieve long-term control with single-agent BCMA BsAbSafety profile3. RELAPSED/REFRACTORY MULTIPLE MYELOMACAMMA-1Phase 1b randomized dose-expansion study of cevostamab (FcRH5×CD3 bispecific) combined with pomalidomide-dexamethasone in BCMA-naïve patients with median 2 prior lines of therapy.Discussion Points:Efficacy and safety resultsPositioning in treatment paradigmUse before BCMA BsAbs?Sonrotoclax + Dexamethasone in t(11;14) R/R MMPhase 1/2 study of sonrotoclax (next-generation BCL2 inhibitor) plus dexamethasone as an all-oral regimen in patients with t(11;14) R/R MM (median 3 prior lines, ~75% triple-exposed).Discussion Points:Efficacy including response rate and PFSSafety profileFuture of BCL2 inhibitors in t(11;14) myeloma in the era of BsAbs and CAR TRedirecTT-1Phase 2 trial combining teclistamab + talquetamab in 90 heavily pretreated patients with R/R extraosseous extramedullary disease (84% triple-class refractory, 36% penta-refractory, 20% prior BCMA CAR T).Discussion Points:Response rate and durability in difficult-to-treat populationSafety concerns with dual bispecific combinationOff-label use considerations4. CAR T-CELL THERAPY TOXICITIESCAR T Immune-Related Adverse Events (UPenn Study - Ho et al)Large cohort study of 198 patients (125 cilta-cel, 73 ide-cel) examining all adverse events other than CRS, ICANS, IEC-HS, and IECAHT.Discussion Points:Landscape of CAR T IRAEs: incidence, types, and timingRisk factors identified for CirAEsMechanism of toxicities and role of CD4+ CAR T-cellsClinical implications: Should prophylactic corticosteroids be used? What ALC threshold? Optimal dose/duration? Prospective studies needed?

Éste episodio es patrocinado por HalloCasa, la tarjeta de presentación digital optimizada para SEO dirigida a agentes inmobiliarios. ¿Buscas al agente adecuado sin importar dónde estés?Descubre y conecta con los mejores agentes inmobiliarios del mundo: https://home.hallocasa.com/En este episodio de HalloCasa #236, converso con Dulce Punaro, asesora inmobiliaria certificada de RE/MAX Metrópoli en la Ciudad de México.Dulce nos comparte su visión sobre el mercado inmobiliario en el Centro-Sur de la CDMX, los retos de la gentrificación, los derechos de inquilinos y propietarios, y consejos clave para compradores, vendedores e inversionistas.También hablamos sobre su certificación CRS (Certified Residential Specialist), su experiencia en RE/MAX Global, y su propio método “Paso a Paso”, diseñado para lograr transacciones seguras, sin estrés y con acompañamiento humano.Temas del episodio:00:01:00 – Introducción00:04:40 – La situación inmobiliaria del Centro-Sur de la Ciudad de México00:10:30 – Gentrificación en la CDMX00:15:20 – Derechos de arrendadores e inquilinos00:20:00 – Cómo trabaja RE/MAX en México y a nivel global00:24:00 – Consejos para inversionistas inmobiliarios00:26:00 – Qué es CRS y su importancia00:28:00 – Tendencias del mercado inmobiliario en la CDMX00:30:00 – El método “Paso a Paso” de Dulce Punaro00:39:00 – Conclusión y formas de contactoConecta con Dulce Punaro:  / dulcepunaro    / dulcepunaro  https://hallocasa.com/profile/6308

What's a Government Shutdown and Why Are We In One?A government shutdown happens when Congress fails to pass annual spending bills or a stopgap continuing resolution (CR) to keep agencies funded. No funding = no authority to operate = federal workers furloughed, services paused, and chaos for agencies and contractors.The House has passed a CR that would fund the government through November 21, but the Senate has rejected it three times. That CR keeps spending at current levels and buys Congress more time to negotiate a full budget. Think of it as saying, “We'll work out the details later, but in the meantime, keep the lights on.”So why the rejection? The sticking points are:* Democrats want the bill to include an extension of Affordable Care Act (ACA) subsidies, which are about to expire.* They also want to block the Office of Management and Budget (OMB) from continuing to cut previously appropriated funds—something they see as a power grab.* Senator Rand Paul is the only Republican joining Democrats in opposing the House CR, but most Senate Democrats have voted it down.What Has to Happen to End the Shutdown?There are four main steps to reopening the government:* Negotiate a compromise CR. Either Republicans agree to ACA and OMB language, or Democrats back off.* Secure bicameral agreement. If the Senate changes the bill, it has to go back to the House.* Presidential approval. Trump has hinted he won't sign anything that includes ACA subsidies or limits on the OMB.* Implementation. Once signed, agencies resume normal operations and furloughed workers return.Two likely paths out of the shutdown:* Republicans stand firm → Democrats allow a CR vote without ACA or OMB demands, hoping to negotiate later.* A compromise CR is passed → includes ACA subsidies and OMB limits → enough Senate Democrats back it → risk of Trump veto remains.Why Is This So Complicated?The shutdown highlights a procedural gap between the House and Senate:* In the House, Republicans have a majority and can pass CRs with zero Democratic votes.* In the Senate, most bills need 60 votes to end debate (invoke cloture) and move to a final vote. Republicans don't have the numbers.Republicans could try to change Senate rules—eliminate the filibuster for budget bills and go with a simple majority—but that would be a massive institutional shift with long-term consequences.Until a resolution is reached, the government remains partially closed and the policy fight over ACA funding and executive power continues.What Happens If Republicans Do Make the Change?If Senate Republicans decide to invoke the so-called “nuclear option”—changing the chamber's rules to eliminate the 60-vote threshold for spending bills—the legislative and political landscape could shift immediately and dramatically.Immediate consequences:Republicans could pass the House-approved continuing resolution with no Democratic support, reopening the government on their terms. That means no extension of ACA subsidies, no restrictions on the Office of Management and Budget, and no need to negotiate across the aisle.Medium-term effects:The rule change would permanently alter how Congress handles appropriations. Any party with a Senate majority and House control could pass funding bills unilaterally, sidestepping the need for bipartisan coalitions. This could speed up the process—but also deepen partisan divides in budget negotiations.Long-term implications:Effectively, it would mean the end of the filibuster for all spending legislation. Shutdowns might become less frequent, since fewer votes are needed to keep the government open—but funding priorities could swing wildly every time control of Congress changes hands. One Congress could expand programs and hike spending; the next could cut deeply, all with a simple majority.In short, while the nuclear option would solve the immediate standoff, it would reshape the Senate's role in fiscal policymaking—and shift power further toward the majority party.Why Can't Republicans Just Pass a Budget Bill?If you've been hearing people say, “Just pass it as a budget bill—no filibuster needed,” here's why that's not happening.The Senate does have a special process called budget reconciliation, which allows certain bills to pass with just 51 votes—no filibuster, no 60-vote threshold. But there are some important catches:* It can only be used once per fiscal year.Technically, reconciliation instructions can cover three areas—spending, revenue, and the debt limit—but Congress usually combines them into a single package. That bill has already been used this year (for the “One Big Beautiful Bill Act”), so the reconciliation tool is off the table until the next fiscal year.* The content of the bill is strictly limited.Under the Byrd Rule, reconciliation bills must directly relate to taxing or spending. Any provision that doesn't have a direct budgetary effect, or that increases the deficit beyond a 10-year window, gets stripped out—or the whole bill risks being disqualified.That's why the current CR probably couldn't go through reconciliation even if that option remained available this fiscal year. It likely includes provisions that violate the Byrd Rule—and certainly would if the OMB limitation Democrats want was included. Those elements either aren't strictly budgetary or would impact the long-term deficit.So even though Republicans hold a Senate majority, they can't simply slap a “budget” label on this bill and pass it with 51 votes. That procedural door is closed for now.If they want to bypass the filibuster, their only real option would be to change Senate rules—a dramatic move that would eliminate the 60-vote requirement for spending bills altogether. Otherwise, they'll need to cut a deal that clears the 60-vote threshold—or accept a prolonged shutdown.That is the current state of the shutdown – we'll see you back here on Monday for our usual daily news shows. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.minimumcomp.com/subscribe

On today's show, LIVE on https://zeno.fm/radio/thunderous-radio/ 5:06 PM CT, 6:06 PM ET: Shut 'Er Down: Senate again rejects CRs, Federal Govt. stays shut down - Fed audit, emergency Medicaid undercut Dems on illegal immigrant health coverage - Shock poll shows broad majority of Americans reject Democrat push to shut down Federal Govt. - Social Security, airports, food stamps and how you are, or are not affected during a government shutdown? - And, what does the Constitution say about who really controls the power of the Federal Govt. purse and the unnecessary drama both parties create for political gain? - we'll examine. Borderline: Massive Chicago illegal immigration raid targets Tren de Aragua members - Multiple people arrested after Feds uncover massive immigration fraud scheme in Minnesota - we'll explore. Plus, Contending For The Faith: Christians respond to Hillary Clinton's rant about 'certain religion' - Pastor cautions believers to seek churches that call them to greatness and confront the gates of hell - Certain faith group tells Christian pastor to go away after airport invites him to public chapel - we'll examine. And, Philadelphia raises a flag that's the emblem of a brutal, totalitarian regime'! http://www.spreaker.com/show/christian-talk-that-rocks https://christiantalkthatrocks.net or http://christiantalkthatrocks.com #governmentshutdown #Schumer #SpeakerJohnson #powerofthepurse #VPVance #healthcareforillegals #ICE #HillaryClinton #Democrats #Republicans #christianrevival #ErikaKirk #Philidelphia #CRs #Venezuelangangs

Kim Strassel, Potomac Watch columnist for the Wall Street Journal, Fox News Contributor, and author of The Biden Malaise: How America Bounces Back from Joe Biden's Dismal Repeat of the Jimmy Carter Years, joined The Guy Benson Show today to break down Chuck Schumer's government shutdown and why it is directly hurting broad swaths of government workers while giving Vought and the Trump admin an opening for mass firings. Strassel explained why the "collective insanity" of the left has led Democrats to abandon their stance on clean CRs, and how the move is really about coddling the far left so Schumer has a message to run on when facing possible primary challenges. Strassel and Benson also broke down why the assassination of Charlie Kirk is now being used by universities as an excuse to shut down right-wing speech under the guise of "security concerns." Listen to the full interview below! Learn more about your ad choices. Visit podcastchoices.com/adchoices

Show #1120 And Again... ...too late and all brand new. 01. Downtown Mystic - Somebody's Always Doin' Something To Somebody (3:54) (Mystic Highway, Sha-La Music, 2025) 02. Miss Emily – Stand Together, Band Together (5:24) (Medicine, Gypsy Soul Records, 2025) 03. Scott Low - Goin' Down the Road Feelin Bad (2:30) (Grateful Blues, self-release, 2025) 04. Dave Weld & the Imperial Flames - Red Hot Tabasco (3:06) (Bluesin' Through The Years, Delmark Records, 2025) 05. Bob Augustine - I'm In Love (3:28) (Folk-IndieBob, MTS Records, 2025) 06. Bob Corritore & Little Milton - I Want To Be The One (3:37) (Early Blues Sessions, SWMAF/VizzTone Records, 2025) 07. Levi Platero - Lay It Down (4:02) (Leaving This Town, self-release, 2025) 08. Shirley Johnson - Blues Attack (4:29) (Selfish Kind Of Gal, Delmark Records, 2025) 09. Manu Lanvin - Change My Ways (4:57) (Man On A Mission, Gel Production, 2025) 10. Gwyn Ashton - Down & Dirty (3:50) (Grease Bucket, Fab Tone Records, 2025) 11. Billy Branch & The Sons Of Blues - The Harmonica Man (5:47) (The Blues Is My Biography, Rosa's Lounge Records, 2025) 12. Spencer Mackenzie - What You Do (4:28) (Empty Chairs, Gypsy Soul Records, 2025) 13. Dallas Burrow (ft. Ray Wylie Hubbard) - Read 'Em and Weep (3:10) (The Way The West Was Won, Forty Below Records, 2025) 14. LaBek - Seek And Ye Shall Find (4:24) (Trouble Blues, self-release, 2025) 15. Randy Lee Riviere - On My Way Down (4:11) (Farmhand Blues, Wilderness Records, 2025) 16. The Soul Of John Black - Been Gone Too Long (3:45) (Soul Salvation, Yellow Dog Records, 2025) 17. Little Hat - Jelly Jam (3:14) (Rocking This Joint Tonight, CRS, 2025) 18. Bywater Call - Hold Me Down (3:20) (Single, self-release, 2025) 19. Jay Hooks - My Kinda Fine (3:04) (Tequila & Bullets, Joplin Street Records, 2025) 20. Ana Popovic - California Chase (3:28) (Dance To The Rhythm, Electric Heel Records, 2025) 21. Jim Keller - Black Dog (4:02) (End Of The World, Continental Song City, 2025) 22. Mick Clarke - Walking In The Dark (3:32) (Tell The Truth, BGO Records, 1991) Bandana Blues is and will always be a labor of love. Please help Spinner deal with the costs of hosting & bandwidth. Visit www.bandanablues.com and hit the tipjar. Any amount is much appreciated, no matter how small. Thank you.

In this JCO Article Insights episode, Dr. Ece Cal interviews Dr. Martin Wermke, author of the JCO article, "Phase I Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-Like T-Cell Engager Obrixtamig (BI 764532) in Patients With Delta-Like Ligand 3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas." TRANSCRIPT The disclosures for guests on this podcast can be found in the transcript. Dr. Ece Cali: Welcome to this episode of JCO Article Insights. This is Dr. Ece Cali, JCO editorial fellow, and today I am joined by Dr. Martin Wermke, Professor for Experimental Cancer Therapy at Dresden University of Technology, to discuss the manuscript “Phase 1 Dose-Escalation Results for the Delta-Like Ligand 3/CD3 IgG-like T-Cell Engager Obrixtamig in Patients with DLL3+ Small Cell Lung Cancer or Neuroendocrine Carcinomas.” Obrixtamig is a bispecific T-cell engager that binds to DLL3 on tumor cells and CD3 on T-cells. This manuscript presents the phase 1A dose escalation results of Obrixtamig in patients with DLL3+ small cell lung cancer and neuroendocrine carcinomas. In this study, 168 patients were treated with Obrixtamig across four different dosing regimens. 49% of the patients had small cell lung cancer, 42% had extrapulmonary neuroendocrine carcinoma, and 8% had large cell neuroendocrine carcinoma of the lung. Patients received a median of two prior lines of therapy. 33% of the patients had brain metastases at baseline. Of note, this trial did not mandate baseline brain imaging. Maximum tolerated dose was not reached. 88% of the patients experienced a treatment-related adverse event, however, only 3.6% of the patients had to discontinue treatment due to treatment-related AEs, and dose reduction due to treatment-related AEs was documented in 2.4% of the patient population. Similar to the other DLL3-targeted bi-therapies, the most common adverse events included CRS in 57%, dysgeusia in 23%, and pyrexia in 21% of the patients. CRS events were mostly mild. They occurred more frequently in the first two to three doses. 9% of the patients experienced ICANS, of which 3% were graded as Grade 3 or higher. And let's review the efficacy results. Responses were only seen in patients who received 90 microgram per kg or more once weekly or once every three weeks dosing. The objective response rate in patients who received an effective dose was 28%. If we review by tumor type, 21% of the small cell lung cancer patients, 27% of the extrapulmonary neuroendocrine carcinoma patients, and 70% of the large cell neuroendocrine carcinoma patients had objective response. Median duration of response was 8.5 months, though this data is immature due to short follow-up. Dr. Wermke, DLL3-targeted bispecific T-cell engagers are reshaping the treatment landscape of small cell lung cancer. This trial investigates Obrixtamig in other high-grade neuroendocrine tumors as well. Can you put this trial into context for us and explain why it may represent an important step forward? Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to discuss our data today. I think the data with Obrixtamig in small cell lung cancer are largely similar to what has been observed with other bispecific T-cell engagers such as tarlatamab with respect to the response rate and duration. It has, however, been to be mentioned that BI 1438001 had a bit more liberal inclusion criteria than other trials around. You already mentioned the fact that we allowed the inclusion of patients without mandatory brain imaging, which led to some patients having their brain mets been diagnosed during the treatment with obrixtamig and then adding to the progressive disease patients. That is something which was not the case with the tarlatamab trials where you really had to have a brain imaging before, and in the Phase 1 trial you were even required to treat the brain mets before you included the patient. So it is a bit different, more poorest patient population. I think the trial adds on existing data by being the first trial to also include non-SCLC neuroendocrine carcinoma of other origin, for example from the gastrointestinal tract, and also by including large cell neuroendocrine carcinoma of the lung, which is a really hard to treat pulmonary neoplasm which currently lacks any standardized treatment. So that is really a step forward which we will build on in the future. Dr. Ece Cali: And one thing I would note in this trial, only patients with tumor expressing DLL3 were enrolled. Can you tell us a little bit more about this target, DLL3 in the context of neuroendocrine tumors, and does DLL3 expression predict clinical outcomes after treatment with DLL3 BiTEs, or do we actually need other predictive biomarkers for these novel agents? Dr. Martin Wermke: Yeah, thank you. That's a pretty interesting question. First of all, DLL3 is an atypical notch ligand, which is expressed by the majority of neuroendocrine carcinomas, virtually absent on healthy adult tissues. Therefore, turning it really into a bona fide target for T-cell engaging therapies, pretty low risk for on-target off-tumor side effects. We found that in all the patients we screened, we had an expression rate of about 94% in small cell lung cancer, 80% of large cell neuroendocrine carcinoma of the lung were positive, and also about 80% of the extrapulmonary neuroendocrine carcinoma. So it's really a high prevalence. So the fact that we only included DLL3+ tumors still means we included most of the patients that presented with these diseases. I think at the moment there are no data suggesting a clear-cut association between DLL3 expression levels and outcome on DLL3 CD3 T-cell engagers. There's also not a lot published. If you want to find this out for tarlatamab, you have to look into their patent to really see the data, but it's not clear-cut and I'm sure we need other markers to complement that. And I think what probably plays a major role is intrinsic T-cell fitness. So the question how really diseased your T-cells are, how old you are, because age also correlates with the fitness of the immune system, and other patient characteristics such as tumor burden, we've seen all across the board that the higher the tumor burden, the lower the rate of prolonged response is in such trials. And I also think we need to focus on other components of the tumor microenvironment. So see how high the T-cell infiltration with obrixtamig is and how abundant suppressive elements like regulatory T-cells or myeloid-derived suppressive cells are. That is work which is currently being done. Data are emerging, but I don't think that at the moment we have any clear biomarker helping us to select who should not receive DLL3 T-cell engagers. Dr. Ece Cali: Those are great points and there is a lot we need to learn about how to use these novel agents in the future. I'd like to highlight the results in large cell neuroendocrine carcinoma of the lung. The response rate in this group was remarkably high at 70%. Though we should note the small sample size of only 14 patients in this trial. After first line chemoimmunotherapy, current approved options for this population have very modest clinical activity. Given these trial results, how do you envision the field moving forward for patients with large cell neuroendocrine carcinoma? Dr. Martin Wermke: Yeah, I think LCNEC is really an area which urgently needs further improvement of therapeutic standards. At the moment, as I said, there is no real standard. We are usually extrapolating from results we have in small cell lung cancer or non-small cell lung cancer, but I don't think we have too many prospective trials really informing this. Of course, 14 patients is a small sample size, but I think it's still fair to say that we can claim that DLL3 T-cell engagers are not doing worse in LCNEC than they do in SCLC. And that's why I think we really need to move forward clinical trials that are specifically targeting this population. Although I fear a bit that, given the rareness of this disease and the aggressiveness of its phenotype, that this is probably not the main focus of the pharmaceutical industry. So I think it's up to us academic investigators to really come up with investigator-initiated trials trying to fill the knowledge gaps we have here. Dr. Ece Cali: And one more thing that I want to talk about is the accessibility for these drugs. These novel agents are showing real promise in improving outcomes for patients with high-grade neuroendocrine tumors, an area where progress has been limited until very recently. However, as DLL3 BiTEs become more widely used, issues of logistics and access come into sharper focus. With unique toxicities and the specialized monitoring, their use is restricted to certain centers. Looking ahead, what kinds of strategies could help mitigate some of these adverse events or make these treatments more broadly available? Dr. Martin Wermke: Yeah, I think if you look at countries like the United States where tarlatamab has already been approved, we can see how the management strategies are evolving. I've heard about a colleague equipping their patients with thermometers and a pill of Dexamethasone, alongside with a temperature control protocol and clearly instructing them, "If you measure a temperature above a certain level then start taking the Dexamethasone and come back to our office and we're going to take care of you." I think that's one way to move forward. I think we are lucky in a way that CRS usually manifests within the first 24 hours. This was the same in our study, like in the tarlatamab studies. So we really know when the time of trouble is for our patients. And in this time, I think we need to instruct the patients to stay close to the hospital. I don't think we need to hospitalize all of them, but we probably need them to stay in a nearby hotel to be able to reach the emergency room if needed in a short period of time. And I think we can also learn in this strategy how to manage bispecific antibodies from the experience our colleagues in hematology had because they have been using bispecific T-cell engagers for quite some years right now and they developed strategies and networks that were able to successfully treat these patients also on an outpatient basis. And I think that is clearly an experience we need to follow, acknowledging that we are talking about diseases which are much more frequent than the standard hematology indications. Dr. Ece Cali: Thank you so much, Dr. Wermke, for this informative discussion and for sharing your perspective on this evolving field. Dr. Martin Wermke: Yeah, thank you for providing me with the opportunity to talk about data. It was really great being able to share that, and I really think that we are just at the beginning of a new exciting area for the treatment of neuroendocrine carcinomas, and I think much improvement is yet to come for our patients. Dr. Ece Cali: Yes, that's really exciting. And thank you everyone for listening to JCO Article Insights. Please come back for more interviews and article summaries and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Martin Wermke's Disclosures Honoraria: Lilly, Boehringer Ingelheim, SYNLAB, Janssen, Merck Serono, GWT, Amgen, Novartis, Pfizer,  BMS GmbH & Co. KG, Regeneron, MJH/PER, Takeda Consulting or Advisory Role: Bristol-Myers Squib, Novartis, Lilly, Boehringer Ingelheim, ISA Pharmaceuticals, Amgen, immatics, Bayer, ImCheck therapeutics, AstraZeneca, Tacalyx, Regeneron, Daiichi Sankyo Europe GmbH, Zymeworks, PharmaMar, Iovance Biotherapeutics, T-Knife, Genentech Research Funding: Roche Patents, Royalties, Other Intellectual Property Travel, Accommodations, Expenses: Pfizer, Bristol-Myers Squibb, AstraZeneca,  Amgen,  GEMoaB, Sanofi/Aventis, immatics,  Merck Serono, Janssen Oncology, Iovance Biotherapeutics, Daiichi Sankyo Europe GmbH"

Looking for daily inspiration?  Get a quote from the top leaders in the industry in your inbox every morning.   What's the one premier event that brings the global attractions industry together? IAAPA Expo 2025, happening in Orlando, Florida, from November 17th through 21st. From breakthrough technology to world-class networking and immersive education, IAAPA Expo 2025 is where you find possible.  And, just for our audience, you'll save $10 when you register at IAAPA.org/IAAPAExpo and use promo code EXPOAPROSTEN. Don't miss it — we won't!   Ron Romens is the President of Commercial Recreation Specialists (CRS). A lifelong creator and entrepreneur, he's been a welder, butcher, truck driver, concession operator, inventor, founder of RAVE Sports (where he helped introduce the first floating trampoline), and, since 1999, the leader of CRS. From Verona, Wisconsin, CRS has grown to approximately 60 team members, representing dozens of top-tier product lines and offering end-to-end recreation solutions—designing lakes and beaches, curating aqua parks, splash pads, shade, and more for camps, municipalities, attractions, and resorts. In this interview, Ron talks about unstructured play, controlling your experience, and how boredom stimulates creativity. Unstructured play “To me, I think unstructured play, I don't think there's near enough of it nowadays. Everything we have is very structured.” Ron ties his inventor mindset directly to the freedom he experienced outdoors as a kid—“sleeping under the stars, swinging off the rope swing, turning over rocks, catching crawdads.” Those unscripted days formed a template for how CRS designs experiences today: create spaces that invite discovery, not dictate it. Whether it's a floating trampoline evolved into a “floating playground” or a purpose-built lake with active and passive zones, CRS builds environments where guests can self-organize, collaborate, and learn through play. He contrasts this with more static, linear attractions (“chlorine and concrete”), noting that open-water, back-to-nature settings put “grass and sand between people's toes.” The result is cross-generational connection and replayability—like the multigenerational family he watched at a Whoa Zone, all choosing their own challenges and sharing one big, memorable experience together. Controlling your experience “People want to have a little bit more control of their own experience now.” Ron traces a market shift since the late 2000s from passive, ride-centric theming toward participatory recreation—zip lines, ropes courses, and on-water challenge parks where guests set pace, path, and intensity. CRS leans into this demand by curating “best-of-class” equipment and tailoring it to each client's goals—amenity, program tool, or monetized attraction—so guests can choose routes, repeat obstacles, or team up with family members. This philosophy extends to CRS's consulting approach: before selling gear, they back up to the “why.” Who is the audience? What outcomes matter? How will success be measured over one, three, and five years? By aligning design with desired control (from gentle exploration to vigorous challenge), CRS helps owners deliver experiences that feel personal, social, and repeatable. Boredom stimulates creativity “It also gets you into a place where you might even have some boredom. And boredom kind of stimulates creativity as well, especially when you've got a group of kids together.” For Ron, occasional boredom is a feature, not a bug. In nature, what first seems disorderly reveals patterns the longer you stay. Give kids a bucket, shovel, sand, and water and “they'll be there forever… creating new games.” CRS intentionally designs canvases—dynamic lakes, floating courses, beaches—where conditions (wind, water, temperature, crowd mix) change daily, nudging guests to tinker, adapt, and invent. That dynamism inspires the “human spirit,” a core CRS mission. Like skiing after fresh snow versus on ice, the same aqua park feels new each visit. Guests return not just for equipment, but for the open-ended possibilities it unlocks—play that sparks imagination, collaboration, and confidence.   In closing, you can learn more about Commercial Recreation Specialists at crs4rec.com or contact Ron directly at 877-896-8442. This podcast wouldn't be possible without the incredible work of our faaaaaantastic team:   Scheduling and correspondence by Kristen Karaliunas   To connect with AttractionPros: AttractionPros.com AttractionPros@gmail.com AttractionPros on Facebook AttractionPros on LinkedIn AttractionPros on Instagram AttractionPros on Twitter (X)

hVIVO CEO Mo Khan discusses the company's H1 2025 results, the impact of CRO market headwinds, and progress on integrating CRS and Cryostore. He also touches on the strategic value of new Chairman Shaun Chilton and outlines what investors can expect for the rest of the year.

hVIVO PLC chief executive Yamin ‘Mo' Khan talked with Proactive's Stephen Gunnion about the company's unaudited results for the first half of 2025 and its outlook for the remainder of the year. Khan explained that revenue for the period came in at just over £24 million, supported by a diversified mix of services, therapeutics, and clients. He added that EBITDA of around £3 million was “helped by the postponement and cancellation fees that we recognised in the first half of this year, together with some of the operational efficiencies that we have already put in place and disciplined cost management.” Cash at 30 June 2025 stood at just over £23 million, while the weighted contracted order book was about £40 million. He noted that the broader CRO industry has faced macroeconomic and sector headwinds, particularly in the vaccine field, which has led to postponements, cancellations, and longer sales cycles. Despite this, Khan said he believes human challenge trials remain highly relevant and could see stronger adoption as drugmakers look to develop medicines faster and at lower cost. The integration of CRS and Cryo Store has progressed well, delivering cross-selling opportunities and annualised savings. Looking ahead, hVIVO expects to deliver about £47 million in revenue for 2025, with a small single-digit EBITDA loss, and aims to return to growth in 2026. For more interviews and updates, visit Proactive's YouTube channel. Don't forget to like this video, subscribe to the channel, and enable notifications for future content. #hVIVO #ClinicalTrials #HumanChallengeTrials #CRO #BiotechNews #DrugDevelopment #ClinicalResearch #LifeSciences #HealthcareInnovation #ProactiveInvestors

In this episode, Dr Christopher Flowers and Dr John Allan discuss their experience with the use of CD20xCD3 bispecific antibodies in the treatment of patients with relapsed/refractory follicular lymphoma. They also their thoughts on key ongoing clinical trials with bispecific antibodies that they are excited about for their potential to change the standard of care for patients with follicular lymphoma. The overall discussion between these 2 experts includes:Using bispecific antibodies in clinical practice for relapsed/refractory follicular lymphoma, including an overview of the drugs mosunetuzumab, epcoritamab, and odronextamabMonitoring and managing CRS and ICANS when prescribing bispecific antibodies to patients with relapsed/refractory follicular lymphoma Promising ongoing clinical trials with bispecific antibodies for patients with follicular lymphoma, such as EPCORE FL-1 with epcoritamab, OLYMPIA-5 with odronextamab, and SOUNDTRACK-F1 with surovatamigPresenters: Dr Christopher Flowers Division Head, Division of Cancer MedicineChair, Professor, Department of Lymphoma/MyelomaJohn Brooks Williams and Elizabeth Williams Distinguished University Chair in Cancer MedicineMD Anderson Cancer CenterHouston, TexasDr John AllanAssociate Professor of Clinical MedicineDivision of Hematology and Medical OncologyWeill Cornell MedicineNew York, New YorkContent based on an online CME program supported by Regeneron Pharmaceuticals, Inc.

durée : 00:03:33 - Charline explose les faits - par : Charline Vanhoenacker - 29 sociétés de journalistes alertent sur une nouvelle atteinte à la liberté d'informer. Cet été, le ministère de l'Intérieur a donné pour instruction à la police de ne pas tenir compte du statut de journaliste en cas de “violences urbaines”. Vous aimez ce podcast ? Pour écouter tous les autres épisodes sans limite, rendez-vous sur Radio France.

(The Center Square) – With 26 days until the federal government runs out of money, top appropriators have narrowed in on their preferred funding gameplan: push the equivalent of the Senate's three-bill minibus through the House, then let a Continuing Resolution temporarily cover the rest. Approving a CR would mark the fourth time in a row that U.S. lawmakers have punted on funding the government properly, having passed three CRs in fiscal year 2025 to keep government funding essentially on cruise control. Congress is supposed to craft and pass 12 appropriations bills on an annual basis, providing updated funding for federal agencies to spend on programs.Support this podcast: https://secure.anedot.com/franklin-news-foundation/ce052532-b1e4-41c4-945c-d7ce2f52c38a?source_code=xxxxxxFull story: https://www.thecentersquare.com/national/article_89a16630-f91a-4610-b832-b0cb77b1fc6a.html

Jana Kramer, the actress, singer, podcast host, and mother joins us to pull back the curtain on the entertainment industry's less glamorous realities and share how she's found her authentic voice through it all.Jana's story begins with remarkable determination – handing her headshot to a soap opera actor while waitressing in Detroit, then convincing a casting director she lived in New York to land her first role. This fearlessness carried her through roles on Friday Night Lights and One Tree Hill before an unexpected pivot to country music during a writers' strike revealed another dimension of her talent.What makes Jana's perspective so refreshing is her willingness to acknowledge both her strengths and limitations. "I don't have the Carrie Underwood voice," she admits, explaining how she instead leaned into emotional authenticity and stage presence. This honesty extends to her candid revelations about industry politics – from being told her CRS performance caused single failures to restrictions on her acting career while pursuing music. Her observations about women in country radio illuminate persistent gender disparities that continue despite the success of predecessors like Faith Hill and Shania Twain.Beyond career insights, Jana opens up about personal growth through therapy, the challenges of balancing touring with Dancing with the Stars competition, and finding joy in her current focus on acting and podcasting. Her experience hosting multiple weekly podcast episodes echoes our own journey – navigating when to speak candidly versus holding back, and finding purpose in connecting with listeners despite occasional backlash.Whether you're a longtime fan from her One Tree Hill days, discovered her through country radio hits like "I Got the Boy," or are new to her story, Jana's resilience and multifaceted career offer inspiration for anyone navigating creative industries while staying true to themselves. Listen now to this conversation that feels less like an interview and more like friends catching up over coffee – or perhaps a bottle of wine, as Jana would prefer.The Try That in a Small Town Podcast is powered by e|spaces! Redefining Coworking - Exceptional Office Space for Every BusinessAt e|spaces, we offer more than just office space - we provide premium private offices designed for focus and growth. Located in the heart of Music Row, our fully furnished offices, private suites, meeting rooms and podcast studio give you the perfect space to work, create and connect. Ready to elevate your business? Book a tour today at espaces.comFrom the Patriot Mobile studios:Don't get fooled by other cellular providers pretending to share your values or have the same coverage. They don't and they can't!Go to PATRIOTMOBILE.COM/SMALLTOWN or call 972-PATRIOTRight now, get a FREE MONTH when you use the offer code SMALLTOWN.Original BrandsOriginal brands is starting a new era and American domestic premium beer, American made, American owned, Original glory.Join the movement at www.drinkoriginalbrands.comFollow/Rate/Share at www.trythatinasmalltown.com -Browse the merch: https://trythatinasmalltown.com/collections/all -For advertising inquiries, email info@trythatinasmalltown.comThe Try That In A Small Town Podcast is produced by Jim McCarthy and www.ItsYourShow.co

Dive into the intricacies of Iranian Nuclear Power with Kenneth Katzman. Find out more about whether Iran has nuclear bombs, what Russia's role is and whether Russia even plays a role, what Iran's strategic motivations could be, the implications and consequences of the US and Israel's military actions, whether there are Iranian opposition groups, and more!Dr. Katzman is a Senior Advisor at the Soufan Group and a Senior Fellow at the Soufan Center, positions he assumed after retiring in late 2022 from his longtime position as a Senior Middle East Analyst at the Congressional Research Service (CRS). He is also a Senior Research Advisor at the Global Insights Group's Strategic Analysis and Situational Awareness Group. During his CRS career specialising on Iran, U.S. sanctions on Iran, the Arab Gulf states, Iraq, Afghanistan, and Iran-backed regional armed groups, Katzman provided analysis and advice to members of Congress through tailored reports and briefings. On about a dozen occasions, he has testified before various Committees and Subcommittees of Congress. He also participated in numerous congressional delegations to the region at the Member and staff level. During 1996 and again during July 2001 - March 2002, he was assigned to the majority staff of the House Foreign Affairs Committee to work on Middle East issues, organizing hearings and helping to draft legislation such as the Iran Sanctions Act (1996).As a well-known expert on the region, Dr. Katzman has delivered numerous presentations and briefings at conferences and meetings in Washington as well as throughout Europe, Asia, the Middle East, and South and Central Asia. In 1998, he wrote expert working papers on the ballistic missile capabilities of Iran and Iraq for the Commission to Assess the Ballistic Missile Threat to the United States ("Rumsfeld Commission"). In late 1999, and again in 2010, the Atlantic Council published his detailed monographs on U.S. sanctions on Iran. During his CRS career and since retiring, Katzman has been quoted frequently on the region and appeared in many regional media, including Al Jazeera, Al Hurra, Al Arabiya, Asharq News, Al Arabiy, and Al Ghad TV. He has authored articles for organizations including The Atlantic Council, the Gulf International Forum, the Arab Gulf States Institute in Washington, and the Arab Center D.C. He has served on several think-tank working groups and been a consultant to several corporations.The International Risk Podcast brings you conversations with global experts, frontline practitioners, and senior decision-makers who are shaping how we understand and respond to international risk. From geopolitical volatility and organised crime, to cybersecurity threats and hybrid warfare, each episode explores the forces transforming our world and what smart leaders must do to navigate them. Whether you're a board member, policymaker, or risk professional, The International Risk Podcast delivers actionable insights, sharp analysis, and real-world stories that matter. The International Risk Podcast – Reducing risk by increasing knowledge.Follow us on LinkedIn and Subscribe for all our updatesTell us what you liked!

In this episode Harriet and Grahame discuss the recent OECD Report Taking Stock of Progress on Transparency and Exchange of Information for Tax Purposes. The report attempts to take stock of the successes and weaknesses of the international tax information exchange regime. Harriet and Grahame discuss whether the report succeeds and analyse the data within it. Amongst all that they have a slight frolic off into a discussion of whether or not the CRS always applied to crypto currency and whether the fast approaching Crypto Asset Report Framework was really necessary.You can find the report here:https://www.oecd.org/content/dam/oecd/en/publications/reports/2025/07/taking-stock-of-progress-on-transparency-and-exchange-of-information-for-tax-purposes_cf7047a4/afddc8c5-en.pdf

Dans cette édition :Effroi à Tourcoing avec trois fusillades la semaine dernière sur fond de trafic de drogue, la CRS 8 spécialisée dans le maintien de l'ordre a été déployée pour gêner délinquants et trafiquants et rassurer les habitants inquiets.Nouveau règlement de compte à Marseille lié au trafic de stupéfiants, une voiture de police percutée après un refus d'obtempérer et des policiers visés par des jets de projectiles.Le ministre de la Justice Gérald Darmanin présente son projet de réforme pénale visant à réintroduire du bon sens dans le fonctionnement de la justice, avec notamment la suppression du sursis à répétition et le rétablissement des courtes peines de prison.Un cinquième corps retrouvé dans les décombres d'un foyer pour personnes en situation de handicap incendié en Charente.L'Union Européenne s'engage à acheter pour 750 milliards de dollars d'hydrocarbures américains sur 3 ans, une dépendance qui inquiète.La France, l'Allemagne et le Royaume-Uni vont livrer une aide humanitaire à Gaza et pourraient reconnaître un État palestinien.Un nouvel acte antisémite à Toulouse, le Conseil constitutionnel valide la loi contre l'antisémitisme à l'université.Coup de froid sur la Méditerranée avec des températures anormalement basses pour la saison.Le quadruple champion olympique Léon Marchand se qualifie pour les demi-finales du 200m 4 nages, Tadej Pogacar fait l'impasse sur le Tour d'Espagne.Notre équipe a utilisé un outil d'Intelligence artificielle via les technologies d'Audiomeans© pour accompagner la création de ce contenu écrit.Distribué par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

Dans cette édition :Israël déçu par la reconnaissance française d'un État palestinien prévue en septembre à l'ONU, l'ambassadeur israélien critiquant une "soumission de la France à une idéologie inquiétante".La France, l'Allemagne et le Royaume-Uni s'apprêtent à envoyer des aides humanitaires à Gaza, dans un contexte de tensions diplomatiques.Actes antisémites condamnés à Toulouse et Marseille, avec des inscriptions menaçantes et une agression d'une humoriste juive.Déploiement de la CRS 8 à Tourcoing pour tenter de ramener le calme après une série de fusillades.Alerte de Santé publique France sur la hausse des passages aux urgences liés à la consommation de cocaïne.Projet de révision constitutionnelle pour accorder plus d'autonomie à la Corse, un sujet épineux pour le gouvernement.Progression modérée du PIB français au deuxième trimestre, dans un contexte économique incertain.Nouvelles frappes russes en Ukraine, malgré les menaces de sanctions de Donald Trump.Hommage au chanteur Ozzy Osbourne, leader du groupe Black Sabbath, dans sa ville natale de Birmingham.Bons résultats des nageurs français aux championnats du monde de natation à Singapour.Notre équipe a utilisé un outil d'Intelligence artificielle via les technologies d'Audiomeans© pour accompagner la création de ce contenu écrit.Distribué par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

Youtube Video of podcast Shownotes and Links In this episode adamd and Zardus chat with Jeff Huang, Ze Sheng, and Qingxiao Xu from the AIxCC team all_you_need_is_a_fuzzing_brain about their AIxCC final submission. We discuss the innovative use of an AI-focused approach in their CRS. The conversation also highlights the significance of static analysis, performance metrics, and the future of cyber reasoning systems in the context of ongoing advancements in AI. We discuss the importance of local models, strategies for vulnerability detection, and the complexities of patching. Links OS lab

In this episode of Better Edge, Bruce K. Tan, MD, discusses the newest clinical practice guidelines for the surgical management of chronic rhinosinusitis (CRS). Dr. Tan covers how treatment paradigms have evolved over the past 15 years, from antibiotic-centric approaches to multifaceted strategies that recognize CRS as a complex inflammatory condition. He dives into the guidelines' recommendations on diagnoses, biologic therapies and multidisciplinary collaboration. Additionally, Dr. Tan shares insights on future directions for research and the promise of precision medicine in tailoring effective treatments for a range of patient profiles.

In part 2 of our series on gender equality in road races we sit down with Canada Running Series CEO and TCS Toronto Waterfront Marathon race director Charlotte Brookes. After noticing a sharp drop off in female marathon participation post-pandemic, Charlotte and her team at CRS set out to address the decline, with the aim of bringing more gender parity to starting lines across CRS events. At the heart of their initiative has been their "Women's Training Program"  in partnership with Mile2Marathon, offering a free 16-week training plan to all female participants in the marathon and half-marathon events at Toronto Waterfront.Now in it's second year, the program has seen participation quadruple since it's inception in 2024 and with it a growing community of motivated female participants supporting one another on their journey to the finish line this October 19th. Tune in this week to hear more about the work Charlotte and her team at CRS are doing as well as how her own experience as a new mother and runner has given her wider perspective on the needs of female athletes. You can find part 1 of our series here. Thanks to this week's sponsor Altitude Sports. Shop now at Altitude Sports and enjoy up to 20% off your first order with the promo code “shakeout” Click here to order

In this week's episode, we'll learn about a JAK inhibitor to prevent complications of CD19-directed CAR T-cell therapy. In a phase 2 study, itacitinib was well tolerated and demonstrated promising reductions in the incidence of cytokine release syndrome and neurotoxicity. After that: investigators report direct interactions between ChAdOx1 and platelets under arterial shear conditions. Investigators say it's a novel biophysical mechanism that potentially contributes to post-vaccination arterial thrombosis. Finally, we explore lineage switch, an emerging form of acute leukemia relapse with dismal outcomes. It arises rapidly following antigen-targeted immunotherapy, highlighting the importance of advanced methods for detection and treatment.Featured Articles: Itacitinib for the prevention of IEC therapy–associated CRS: results from the 2-part phase 2 INCB 39110-211 studyShear-dependent platelet aggregation by ChAdOx1 nCoV-19 vaccine: a novel biophysical mechanism for arterial thrombosisProject EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of relapse in leukemia

Dans Europe 1 Matin :Invités : Frédéric Ploquin, grand reporter, spécialiste du grand banditisme et auteur du livre "Les réseaux secrets de la police" et Franck Allisio, député Rassemblement National des Bouches du RhôneLes forces de l'ordre tentent d'enrayer le fléau des violences urbaines à Béziers avec le déploiement de la CRS 80 en renfort pour lutter contre le trafic de drogue dans le quartier de la Devez.17 narcotrafiquants parmi les plus dangereux de France passent leur première nuit dans la prison de haute sécurité de Vendin-le-Vieil, un établissement hors normes destiné à accueillir 100 détenus à risque d'ici début août.Le ministre de l'Intérieur Bruno Retailleau durcit le ton et retire les privilèges diplomatiques à 80 dignitaires algériens accusés d'avoir dénigré la France, dans le cadre de la riposte graduée contre l'Algérie.Un Français sur cinq dort moins de 6 heures par nuit, le ministre de la Santé Yannick Neuder annonce 25 préconisations pour lutter contre cette dette de sommeil généralisée.Valentin Paret-Peintre offre la première victoire française sur le Tour de France en s'imposant au sommet du mythique Mont Ventoux, une performance historique.Notre équipe a utilisé un outil d'Intelligence artificielle via les technologies d'Audiomeans© pour accompagner la création de ce contenu écrit.Distribué par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

Dans cette édition :Les forces de l'ordre sont mobilisées à Béziers pour lutter contre le trafic de drogue dans un quartier gangréné par ce fléau, avec le renfort de la CRS 81 qui mène des opérations de fouille dans les logements suspects.17 narcotrafiquants parmi les plus dangereux de France ont été transférés dans la prison de haute sécurité de Vendin-le-Vieil, sous un dispositif sécuritaire hors norme, le ministre de la Justice justifiant ces mesures face à la menace du narcotrafic.Le couple franco-allemand affiche son unité malgré des divergences, notamment sur les questions de défense, l'Allemagne poursuivant ses achats d'armements américains tandis que la France souhaite une Europe plus souveraine.La France exige plus de fermeté de l'Union Européenne dans les négociations avec les États-Unis, menaçant de représailles face à la possibilité de surtaxes douanières.Les États-Unis se retirent de l'UNESCO, accusant l'organisation de promouvoir des causes clivantes et d'être partiale envers Israël, une décision qui s'inscrit dans la politique de retrait de plusieurs agences onusiennes.Notre équipe a utilisé un outil d'Intelligence artificielle via les technologies d'Audiomeans© pour accompagner la création de ce contenu écrit.Distribué par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

Dans cette édition :Les forces de l'ordre tentent de reprendre le contrôle face aux violences urbaines à Béziers, avec le déploiement de la CRS 81 pour lutter contre le trafic de drogue dans la ville.Les 17 premiers narcotrafiquants les plus dangereux de France ont été transférés dans la nouvelle prison de haute sécurité de Vendin-le-Vieil, sous haute surveillance.Le ministre de la Justice justifie la mise en place de ce dispositif carcéral exceptionnel pour lutter contre le narcotrafic et la criminalité organisée.En France, l'absentéisme au travail atteint des niveaux record, poussant le gouvernement à envisager des réformes du système d'indemnisation des arrêts maladie.Valentin Paret-Peintre, un coureur français, remporte une victoire historique sur le mythique Mont Ventoux lors du Tour de France.Notre équipe a utilisé un outil d'Intelligence artificielle via les technologies d'Audiomeans© pour accompagner la création de ce contenu écrit.Distribué par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

Dans cette édition :Retour au calme précaire dans le quartier de la Devez à Béziers après des émeutes liées au trafic de drogue, grâce à l'intervention d'une unité de CRS spécialisée dans la lutte contre les violences urbaines.Transfert de 17 narcotrafiquants particulièrement dangereux vers la prison ultra-sécurisée de Vendin-le-Vieil, dans le cadre d'un plan visant à regrouper 100 détenus à risque dans une véritable forteresse carcérale.Sanctions du ministre de l'Intérieur Bruno Retailleau contre des dignitaires algériens ayant dénigré la France, dans un contexte de tensions diplomatiques entre les deux pays.Inquiétude des habitants de Béziers quant au départ annoncé des renforts policiers, craignant le retour des trafiquants de drogue.Dégradation de la qualité du sommeil des Français, avec un Français sur cinq dormant moins de 6 heures par nuit, selon les recommandations des experts.Notre équipe a utilisé un outil d'Intelligence artificielle via les technologies d'Audiomeans© pour accompagner la création de ce contenu écrit.Distribué par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

Welcome to this episode of The Oncology Brothers! Drs. Rahul and Rohit Gosain dived into the complexities of relapsed refractory diffuse large B-cell lymphoma (DLBCL) with their new series focused on challenging real-life cases. In this episode, we are joined by esteemed guests Dr. Carla Casulo from Wilmot Cancer Center and Dr. Tara Graff from Mission Cancer and Blood Center. Together, we explored the current standard of care, including R-CHOP and the role of bi-specific antibodies like epcoritamab and glofitimab. Key topics covered included: • When to use bi-specific antibodies and how to manage side effects • The importance of MRD monitoring in treatment decisions • Insights on patient management in community oncology settings • The evolving landscape of treatment options for DLBCL, including CAR-T therapy and clinical trials We also discuss practical considerations for community oncologists, including the management of cytokine release syndrome (CRS) and the role of immunoglobulin therapy in patients with low IgG levels. Whether you're a healthcare professional or someone interested in the latest advancements in oncology, this episode is packed with valuable insights and expert opinions. YouTube: https://youtu.be/05ieIyAIx_8 Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and share your thoughts in the comments! Let us know if there are specific scenarios you'd like us to cover in future episodes.

Dans cette édition :Retour au calme dans le quartier de Val-de-l'Aurence à Limoges après le déploiement de la brigade CRS 82 pour faire face aux violences des nuits précédentes.Guet-apens organisé par une cinquantaine de personnes contre des policiers à Béziers, en réaction à des interpellations et saisies de drogue dans le quartier de la Devèze.Début des opérations de transfert des narcotrafiquants les plus dangereux vers la prison de haute sécurité de Vendin le Vieil, sécurisée pour empêcher toute communication avec l'extérieur.Violences communautaires dans la province de Soueïda en Syrie, faisant 1000 morts et 130 000 déplacés en une semaine.Naufrage d'un bateau de tourisme dans la Baie d'Halong au Vietnam, faisant au moins 38 morts.Difficultés financières du groupe Gifi, enseigne de déco et cadeaux, qui prévoit de supprimer 300 postes, dont plus de la moitié à Villeneuve-sur-Lotte.Victoires de Tim Wellens sur le Tour de France et de Loïs Boisson au tournoi d'Hambourg.Notre équipe a utilisé un outil d'Intelligence artificielle via les technologies d'Audiomeans© pour accompagner la création de ce contenu écrit.Distribué par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

Plusieurs débats au cœur de l'actualité, les Grandes gueules ont le choix, en débattre ou non : 180 300 euros à des CRS, Mbappé soupçonné de pots de vin Bientôt le droit de vote à 16 ans au Royaume-Uni ! 29 ans, âge moyen pour un premier enfant en France

Send us a textDo you have CRS like we do?We might have gotten heat stroke, but you still got your episode! Daniel forgets Dr. Jones and Marcus can't remember anything. Wear protective clothing to protect you from the sun's harmful rays. Support the show

7/1/25 6am CT Hour - Mark Mastroianni/ Art Wigchers John and Sarah chat about Big Beautiful Bill, conviction of Idaho murderer, US Postage Stamps and holiday travel. Mark breaks down where AI is going next and Pope Leo's guidelines for ethics when it comes to tech. Art shares how he became involved with CRS and the education of girls in Ethiopia. https://crs.donordrive.com/girlsgain

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss important advances in the treatment of prostate, bladder, and kidney cancers that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News.  I am delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of the GU Center at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that were presented at the 2025 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode.  Jeanny, it is great to have you on the podcast. Dr. Jeanny Aragon-Ching: Oh, thank you so much, Neeraj. Dr. Neeraj Agarwal: Jeanny, let's begin with some prostate cancer abstracts. Let's begin with Abstract 5017 titled, “Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer.” Can you walk us through the design and the key findings of this first-in-human trial? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this study, presented by Dr. Capucine Baldini, introduces pasritamig, a first-in-class T-cell redirecting bispecific antibody that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. KLK2 is also known as human kallikrein 2, which is selectively expressed in prostate tissue. And for reference, KLK3 is what we now know as the PSA, prostate-specific antigen, therefore making it an attractive and specific target for therapeutic engagement. Now, while this was an early, first-in-human, phase 1 study, it enrolled 174 heavily pretreated metastatic CRPC patients. So many were previously treated with ARPIs, taxanes, and radioligand therapy. So given the phase 1 nature of this study, the primary objective was to determine the safety and the RP2D, which is the recommended phase 2 dose. Secondary objectives included preliminary assessment of antitumor activity. So, pasritamig was generally well tolerated. There were no treatment-related deaths. Serious adverse events were rare. And in the RP2D safety cohort, where patients received the step-up dosing up to 300 mg of IV every 6 weeks, the most common treatment-related adverse events were low-grade infusion reactions. There was fatigue and grade 1 cytokine release syndrome, what we call CRS. And no cases of neurotoxicity, or what we call ICANS, the immune effector cell-associated neurotoxicity syndrome, reported. Importantly, the CRS occurred in just about 8.9% of patients. All were grade 1. No patients required tocilizumab or discontinued treatment due to adverse events. So, this suggests a favorable safety profile, allowing hopefully for outpatient administration without hospitalization, which will be very important when we're thinking about bispecifics moving forward. In terms of efficacy, pasritamig showed promising activity. About 42.4% of evaluable patients achieved a PSA50 response. Radiographic PFS was about 6.8 months. And among patients with measurable disease, the objective response rate was about 16.1% in those with lymph node or bone metastases, and about 3.7% in those with visceral disease, with a median duration of response of about 11.3 months. So, altogether, this data suggests that pasritamig may offer a well-tolerated and active new potential option for patients with metastatic CRPC.   Again, as a reminder, with the caveat that this is still an early phase 1 study. Dr. Neeraj Agarwal: Thank you, Jeanny. These are promising results for a bispecific T-cell engager, pasritamig, in prostate cancer. I agree, the safety and durability observed here stand out, and this opens the door for further development, possibly even in earlier disease settings.  So, shifting now from immunotherapy to the evolving role of genomics in prostate cancer. So let's discuss Abstract 5094, a real-world, retrospective analysis exploring the prognostic impact of homologous recombination repair gene mutations, especially BRCA1 and BRCA2 mutations, in metastatic hormone-sensitive prostate cancer. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So this study was presented by Dr. David Olmos, represents one of the largest real-world analyses we have evaluating the impact of homologous recombination repair, or what we would call HRR, alterations in metastatic hormone-sensitive prostate cancer. So, this cohort included 556 men who underwent paired germline and somatic testing. Now, about 30% of patients had HRR alterations, with about 12% harboring BRCA1 or BRCA2 mutations and 16% having alterations in other HRR genes. Importantly, patients were stratified via CHAARTED disease volume, and outcomes were examined across treatment approaches, including ADT alone, doublet therapy, and triplet therapy. The prevalence of BRCA and HRR alterations were about similar between the metastatic hormone-sensitive prostate cancer and the metastatic castrate-resistant prostate cancer, with no differences observed, actually, between the patients with high volume versus low volume disease.  So, the key finding was that BRCA and HRR alterations were associated with poor clinical outcomes in metastatic hormone-sensitive prostate cancer. And notably, the impact of these alterations may actually be even greater in metastatic hormone-sensitive prostate cancer than previously reported in metastatic CRPC. So, the data showed that when BRCA mutations are present, the impact of the volume of disease is actually limited. So, poor outcomes were observed across the board for both high-volume and low-volume groups. So, the analysis showed that patients with HRR alterations had significantly worse outcomes compared to patients without HRR alterations. Median radiographic progression-free survival was about 20.5 months for the HRR-altered patients versus 30.6 months for the non-HRR patients, with a hazard ratio of 1.6. Median overall survival was 39 months for HRR-altered patients compared to 55.7 months for the non-HRR patients, with a hazard ratio of 1.5. Similar significant differences were observed when BRCA-mutant patients were compared with patients harboring non-BRCA HRR mutations. Overall, poor outcomes were independent of treatment of ARPI or taxanes. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data reinforce homologous recombination repair mutations as both a predictive and prognostic biomarker, not only in the mCRPC, but also in the metastatic hormone-sensitive setting as well. It also makes a strong case for incorporating genomic testing early in the disease course and not waiting until our patients have castration-resistant disease. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. And I think this really brings home the point and the lead up to the AMPLITUDE trial, which is LBA5006, a phase 3 trial that builds on this very concept of testing with a PARP inhibitor, niraparib, in the hormone-sensitive space. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the AMPLITUDE trial, a phase 3 trial presented by Dr. Gerhardt Attard, enrolled 696 patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. 56% of these patients had BRCA1 and BRCA2 mutations. Patients were randomized to receive abiraterone with or without niraparib, a PARP inhibitor. The majority of patients, 78% of these patients, had high-volume metastatic hormone-sensitive prostate cancer, and 87% of these patients had de novo metastatic HSPC. And 16% of these patients received prior docetaxel, which was allowed in the clinical trial. So, with a median follow-up of nearly 31 months, radiographic progression-free survival was significantly prolonged with the niraparib plus abiraterone combination, and median was not reached in this arm, compared to abiraterone alone, which was 29.5 months, with a hazard ratio of 0.63, translating to a 37% reduction in risk of progression or death. This benefit was even more pronounced in the BRCA1 and BRCA2 subgroup, with a 48% reduction in risk of progression, with a hazard ratio of 0.52. Time to symptomatic progression also improved significantly across all patients, including patients with BRCA1, BRCA2, and HRR mutations. Although overall survival data remain immature, early trends favored the niraparib plus abiraterone combination. The safety profile was consistent with prior PARP inhibitor studies, with grade 3 or higher anemia and hypertension were more common but manageable. Treatment discontinuation due to adverse events remained low at 11%, suggesting that timely dose modifications when our patients experience grade 3 side effects may allow our patients to continue treatment without discontinuation. These findings support niraparib plus abiraterone as a potential new standard of care in our patients with metastatic hormone-sensitive prostate cancer with HRR alterations, and especially in those who had BRCA1 and BRCA2 mutations. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. This trial is especially exciting because it brings PARP inhibitors earlier into the treatment paradigm. Dr. Neeraj Agarwal: Exactly. And it is exciting to see the effect of PARP inhibitors in the earlier setting.  So Jeanny, now let's switch gears a bit to bladder cancer, which also saw several impactful studies. Could you tell us about Abstract 4502, an exploratory analysis from the EV-302 trial, which led to approval of enfortumab vedotin plus pembrolizumab for our patients with newly diagnosed metastatic bladder cancer? So here, the authors looked at the outcomes in patients who achieved a confirmed complete response with EV plus pembrolizumab. Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, EV-302 demonstrated significant improvements in progression-free and overall survival for patients previously treated locally advanced or metastatic urothelial cancer, I'll just call it metastatic UC, as a frontline strategy, establishing EV, which is enfortumab vedotin, plus pembro, with pembrolizumab as standard of care in this setting.  So, this year at ASCO, Dr Shilpa Gupta presented this exploratory responder analysis from the phase 3 EV-302 trial. Among 886 randomized patients, about 30.4% of patients, this is about 133, in the EV+P arm, and 14.5% of the patients in the chemotherapy arm, achieved a confirmed complete response. They call it the CCR rates. So for patients who achieved this, median PFS was not reached with EV+P compared to 26.9 months with chemotherapy, with a hazard ratio of 0.36, translating to a 64% reduction in the risk of progression. Overall survival was also improved. So the median OS was not reached in either arm, but the hazard ratio favored the EV+P at 0.37, translating to a 63% reduction in the risk of death. The median duration of complete response was not reached with EV+P compared to 15.2 months with chemotherapy. And among those patients who had confirmed CRs at 24 months, 78% of patients with the EV+P arm remained progression-free, and around 95% of the patients were alive, compared to 54% of patients who were progression-free and 86% alive of the patients in the chemotherapy arm. Safety among responders were also consistent with prior reports. Grade 3 or higher treatment-related adverse events occurred in 62% of EV+P responders and 72% of chemotherapy responders. Most adverse events were managed with dose modifications, and importantly, no treatment-related deaths were reported among those who were able to achieve complete response.  So these findings further reinforce EV and pembro as the preferred first-line therapy for metastatic urothelial carcinoma, offering a higher likelihood of deep, durable responses with a fairly manageable safety profile. Dr. Neeraj Agarwal: Thank you for the great summary, Jeanny. These findings underscore the depth and durability of responses achievable with this combination and also suggest that achieving a response may be a surrogate for long-term benefit in patients with metastatic urothelial carcinoma.  So now, let's move to Abstract 4503, an exploratory ctDNA analysis from the NIAGARA trial, which evaluated perioperative durvalumab, an immune checkpoint inhibitor, in muscle-invasive bladder cancer. So what can you tell us about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in NIAGARA, presented by Dr. Tom Powles, the addition of perioperative durvalumab to neoadjuvant chemotherapy, gem/cis, significantly improved event-free survival, overall survival, and pathologic complete response in patients with cisplatin-eligible muscle-invasive bladder cancer. Recall that this led to the U.S. FDA approval of this treatment regimen on March 28, 2025.  So, a planned exploratory analysis evaluated the ctDNA dynamics and their association with clinical outcomes, which was the one presented recently at ASCO. So, the study found that the incidence of finding ctDNA positivity in these patients was about 57%. Following neoadjuvant treatment, this dropped to about 22%, with ctDNA clearance being more common in the durvalumab arm, about 41%, compared to the chemotherapy control arm of 31%. Notably, 97% of patients who remained ctDNA positive prior to surgery failed to achieve a pathologic CR. So, this indicates a strong association between ctDNA persistence and lack of tumor eradication. So, postoperatively, only about 9% of patients were ctDNA positive. So, importantly, durvalumab conferred an event-free survival benefit regardless of ctDNA status at both baseline and post-surgery. Among patients who were ctDNA positive at baseline, durvalumab led to a hazard ratio of 0.73 for EFS. So, this translates to a 27% reduction in the risk of disease recurrence, progression, or death compared to the control arm. In the post-surgical ctDNA-positive group, the disease-free survival was also improved with a hazard ratio of 0.49, translating to a 51% reduction in the risk of recurrence.  So, these findings underscore the prognostic value of ctDNA and suggest that durvalumab provides clinical benefit irrespective of molecular residual disease status. So, the data also supports that ctDNA is a promising biomarker for future personalized strategies in the perioperative treatment of muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Jeanny. It is great to see that durvalumab is improving outcomes in these patients regardless of ctDNA status. However, based on these data, presence of ctDNA in our patients warrants a closer follow-up with imaging studies, because these patients with positive ctDNA seem to have a higher risk of recurrence. Dr. Jeanny Aragon-Ching: I agree, Neeraj.  Let's round out the bladder cancer discussion with Abstract 4518, which reported the interim results of SURE-02, which is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure, Jeanny. So, Dr Andrea Necchi presented interim results from the SURE-02 trial. This is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by a response-adapted bladder-sparing treatment and adjuvant pembrolizumab in patients with muscle-invasive bladder cancer.  So, in this interim analysis, 40 patients were treated and 31 patients were evaluable for efficacy. So, the clinical complete response rate was 38.7%. All patients achieving clinical complete response underwent bladder-sparing approach with a repeat TURBT instead of radical cystectomy. Additionally, 51.6% of patients achieved excellent pathologic response with a T stage of 1 or less after neoadjuvant therapy. The treatment was well tolerated, with only 12.9% of patients experiencing grade 3 or higher adverse events without needing dose reduction of sacituzumab. Molecular profiling, interestingly, showed that clinical complete response correlated with luminal and genomically unstable subtypes, while high stromal gene expression was associated with lack of response.  These results suggest that sacituzumab plus pembrolizumab combination has promising activity in this setting, and tolerability, and along with other factors may potentially allow a bladder preservation approach in a substantial number of patients down the line. Dr. Jeanny Aragon-Ching: Yeah, agree with you, Neeraj. And the findings are very provocative and support completing the full trial enrollment and further exploration of this strategy in muscle-invasive bladder cancer in order to improve and provide further bladder-sparing strategies. Dr. Neeraj Agarwal: Agree. So, let's now turn to the kidney cancer, starting with Abstract 4505, the final overall analysis from CheckMate-214 trial, which evaluated nivolumab plus ipilimumab, so dual checkpoint inhibition strategy, versus sunitinib in our patients with metastatic clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So, the final 9-year analysis of the phase 3 CheckMate-214 trial confirms the long-term superiority of nivolumab and ipilimumab over sunitinib for first-line treatment of advanced metastatic renal cell carcinoma. So, this has a median follow-up of 9 years. Overall survival remains significantly improved with the combination. So, in the ITT patient population, the intention-to-treat, the hazard ratio for overall survival was 0.71. So, this translates to a 29% reduction in the risk of death. 31% of patients were alive at this 108-month follow-up compared to 20% only in those who got sunitinib. So, similar benefits were observed in the intermediate- and poor-risk groups with a hazard ratio of 0.69, and 30% versus 19% survival at 108 months.  Importantly, a delayed benefit was also seen in those favorable-risk patients. So, the hazard ratio for overall survival improved from 1.45 in the initial report and now at 0.8 at 9 years follow-up, with 35% of patients alive at 108 months compared to 22% in those who got sunitinib. Progression-free survival also favored the nivo-ipi arm across all risk groups. At 96 months, the probability of remaining progression-free was about 23% compared to 9% in the sunitinib arm in the ITT patient population, 25% versus 9% in the intermediate- and poor-risk patients, and 13% compared to 11% in the favorable-risk patients. Importantly, at 96 months, 48% of patients in the nivo-ipi responders remained in response compared to just 19% in those who got sunitinib. And in the favorable-risk group, 36% of patients who responded remained in response, although data were not available for sunitinib in this subgroup.  So, this data reinforces the use of nivolumab and ipilimumab as a durable and effective first-line effective strategy for standard of care across all risk groups for advanced renal cell carcinoma. Dr. Neeraj Agarwal: Thank you, Jeanny. And of course, since ipi-nivo data were presented, several other novel ICI-TKI combinations have emerged. And I'm really hoping to see very similar data with TKI-ICI combinations down the line. It is really important to note that we are not seeing any new safety signals with the ICI combinations or ICI-based therapies, which is very reassuring given the extended exposure. Dr. Jeanny Aragon-Ching: Absolutely agree with you there, Neeraj.  Now, going on and moving on to Abstract 4514, which is the KEYNOTE-564 trial, and they reported on the 5-year outcomes of adjuvant pembrolizumab in clear cell RCC in patients who are at high risk for recurrence. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the KEYNOTE-564 trial established pembrolizumab monotherapy as the first adjuvant regimen to significantly improve both disease-free survival and overall survival compared to placebo after surgery for patients with clear cell renal cell carcinoma. So, Dr Naomi Haas presented the 5-year update from this landmark trial.  A total of 994 patients were randomized to receive either pembrolizumab or placebo. The median follow-up at the time of this analysis was approximately 70 months. Disease-free survival remained significantly improved with pembrolizumab. The median DFS was not reached with pembrolizumab compared to 68.3 months with placebo, with a hazard ratio of 0.71, translating to a 29% reduction in risk of recurrence. At 5 years, 60.9% of patients receiving pembrolizumab remained disease-free compared to 52.2% with placebo. Overall survival also favored pembrolizumab. The hazard ratio for OS was 0.66, translating to a 34% reduction in risk of death, with an estimated 5-year overall survival rate of 87.7% with pembrolizumab compared to 82.3% for placebo. Importantly, these benefits were consistent across all key subgroups, including patients with sarcomatoid features. In addition, no new serious treatment-related adverse events have been reported in the 3 years since treatment completion.  So, these long-term data confirm pembrolizumab as a durable and effective standard adjuvant therapy for patients with resected, high-risk clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Thank you for that wonderful summary, Neeraj. Dr. Neeraj Agarwal: That wraps up our kidney cancer highlights. Any closing thoughts, Jeanny, before we conclude? Dr. Jeanny Aragon-Ching: It's been so wonderful reviewing these abstracts with you, Neeraj. So, the 2025 ASCO Annual Meeting showcased a lot of transformative data across GU cancers, from first-in-class bispecifics to long-term survival in RCC. And these findings are already shaping our clinical practices. Dr. Neeraj Agarwal: I agree. And we have covered a broad spectrum of innovations in GU cancers with strong clinical relevance.  So, thank you, Jeanny, for joining me today and sharing your insights.  And thank you to our listeners for joining us. You will find links to the abstracts discussed today in the transcript of this episode. If you find these conversations valuable, please take a moment to rate, review, and subscribe to the ASCO Daily News Podcast wherever you listen. Thank you so much. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:    Dr. Neeraj Agarwal     @neerajaiims     Dr. Jeanny Aragon-Ching   Follow ASCO on social media:       @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn       Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono   Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,    Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:    Dr. Vamsi Velcheti   @VamsiVelcheti    Dr. Nathan Pennell   @n8pennell   Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn   ASCO on BlueSky   Disclosures:   Dr. Vamsi Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:     Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron    Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

中国人民银行与香港金融管理局于6月20日联合宣布，内地与香港快速支付系统互联互通（下称跨境支付通）将于6月22日正式上线。届时，两地居民仅凭收款方手机号码或银行账户，即可完成小额跨境汇款的实时到账操作，突破传统跨境汇款的时效限制。 当前，首批参与跨境支付通共12家，其中内地机构包括工、农、中、建、交五家国有大行以及招商银行；香港机构包括中银香港、东亚银行、建银亚洲、恒生银行、汇丰香港、工银亚洲，后续将逐步扩大参与范围。 02:13 跨境支付通：6月22号后的转账变革，速度与手续费的双重颠覆！ 05:26 招行和交行的转账体验对比：方便快捷但有限额 10:53 在四大上班，每个月给女儿汇款一万元生活费，养儿育女的现实与劝退 16:23 “信用卡额度限制：生活使用与投资之间的尴尬选择” 21:49 揭开CRS的神秘面纱：中国税务机关如何掌握境外信息 27:16 揭秘FATCA：美国与中国之间的双向信息交换机制 32:48 香港银行卡与人民币支付的便利性：在内地和香港之间的无缝连接 38:16 海外投资的机遇与挑战：普通百姓如何实现资产增值？ 43:42 创业者的必备心态：百万大火 Origin Story 49:10 A股投资策略：技术分析、基本面分析与基本面认知的重要性 54:39 投资理念与经历：在旅途中寻找优质股票的故事 01:00:04 情绪价值与实际收益：理财中的幻觉与现实差距

中国人民银行与香港金融管理局于6月20日联合宣布，内地与香港快速支付系统互联互通（下称跨境支付通）将于6月22日正式上线。届时，两地居民仅凭收款方手机号码或银行账户，即可完成小额跨境汇款的实时到账操作，突破传统跨境汇款的时效限制。 当前，首批参与跨境支付通共12家，其中内地机构包括工、农、中、建、交五家国有大行以及招商银行；香港机构包括中银香港、东亚银行、建银亚洲、恒生银行、汇丰香港、工银亚洲，后续将逐步扩大参与范围。 02:13 跨境支付通：6月22号后的转账变革，速度与手续费的双重颠覆！ 05:26 招行和交行的转账体验对比：方便快捷但有限额 10:53 在四大上班，每个月给女儿汇款一万元生活费，养儿育女的现实与劝退 16:23 “信用卡额度限制：生活使用与投资之间的尴尬选择” 21:49 揭开CRS的神秘面纱：中国税务机关如何掌握境外信息 27:16 揭秘FATCA：美国与中国之间的双向信息交换机制 32:48 香港银行卡与人民币支付的便利性：在内地和香港之间的无缝连接 38:16 海外投资的机遇与挑战：普通百姓如何实现资产增值？ 43:42 创业者的必备心态：百万大火 Origin Story 49:10 A股投资策略：技术分析、基本面分析与基本面认知的重要性 54:39 投资理念与经历：在旅途中寻找优质股票的故事 01:00:04 情绪价值与实际收益：理财中的幻觉与现实差距

Dr. John Sweetenham and Dr. Marc Braunstein highlight top research on hematologic malignancies from the 2025 ASCO Annual Meeting, including abstracts on newly diagnosed chronic phase CML, relapsed B-cell lymphoma, and multiple myeloma. Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. On today's episode, we'll be discussing promising advances in newly diagnosed chronic phase CML, relapsed B-cell lymphoma, multiple myeloma, and other hematologic malignancies that were presented at the 2025 ASCO Annual Meeting. Joining me for this discussion is Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center. Our full disclosures are available in the transcript of this episode.  Marc, there were some great studies in the heme space at this year's Annual Meeting, and it's great to have you back on the podcast to highlight some of these advances. Dr. Marc Braunstein: Yes, I agree, John, and thank you so much for inviting me again. It's great to be here.  Dr. John Sweetenham: Let's start out with Abstract 6501. This was a study that reported on the primary endpoint results of the phase 3B ASC4START trial, which assessed asciminib versus nilotinib in newly diagnosed chronic phase CML. And the primary endpoint of this, as you know, was time to treatment discontinuation because of adverse events. Can you give us your insights into this study? Dr. Marc Braunstein: Absolutely. So, like you mentioned, you know, asciminib is an allosteric inhibitor of the BCR-ABL kinase that has activity in CML, and that includes patients with the T315I mutation that confers resistance to first- and second-generation TKIs. So, the ASC4FIRST study, which was published last year in the New England Journal of Medicine, showed superior efficacy of asciminib compared to investigator-selected first- or second-generation TKIs, actually leading to the FDA approval of asciminib in first-line CML. So, the authors of that study presented data at this year's ASCO meeting from the phase 3 ASC4START comparing safety and time to discontinuation due to adverse events of asciminib versus nilotinib, a second-generation TKI. So, 568 patients with newly diagnosed CML were randomized one-to-one to once-daily asciminib or twice-daily nilotinib. So, at a median follow-up of 9.7 months, about 11% in the asciminib group and 17% in the nilotinib group discontinued treatment, with significantly fewer discontinuations with asciminib due to adverse events. There was also a secondary endpoint of major molecular response, which was also better with asciminib. For example, the MR 4.5, which is a deep response, was 2.5% versus 0.4% favoring asciminib by week 12. So, I think in conclusion, these results build on the ASC4FIRST study, making the case for the superior safety and efficacy of asciminib versus other first- or second-generation TKIs in newly diagnosed CML. Dr. John Sweetenham: Thanks, Marc. Do you think this is going to change practice? Dr. Marc Braunstein: I think so. I think there are still some questions to be answered, such as what resistance mutations occur after first-line treatment with asciminib. But I think the sum of these studies really make the case for using asciminib upfront in CML. Dr. John Sweetenham: Okay, great. Thank you. And let's move on to our second abstract. This was Abstract 7015 and was reported from Mass General Hospital. And this was a study in patients with relapsed and refractory diffuse large B-cell lymphoma and reported the 2-year results of the so-called STARGLO study. This is a comparison of glofitamab, a T-cell engaging bispecific antibody, with gemcitabine and oxaliplatin in this group of patients. Can you tell us a little bit about your impressions of this study? Dr. Marc Braunstein: Absolutely. So just for background, the treatment landscape for relapsed/refractory large B-cell lymphoma is expanding, now with two bispecific antibodies targeting CD20 that are approved after two or more lines of therapy. Among these, glofitamab was approved in 2023 based on phase 2 data showing an objective response rate of 52%, with 39% complete responses in relapsed/refractory large B-cell lymphoma patients after a median of three prior lines of therapy. Distinguishing glofitamab from epcoritamab, the other approved bispecific, glofitamab was given for 12 cycles and then stopped. Additionally, when combined with gemcitabine and oxaliplatin in the phase 3 STARGLO study, there was significantly improved overall survival compared to rituximab plus gemcitabine and oxaliplatin in transplant-ineligible relapsed/refractory large B-cell lymphoma patients at a median follow-up of 11 months.  The authors of that study published last year in Lancet now present at ASCO this year the 2-year follow-up of the STARGLO study. Two hundred and seventy-four patients with a median of one prior line of therapy were randomized two-to-one to glofitamab plus GemOx versus rituximab plus GemOx, with the primary endpoint of overall survival. Here, the median overall survival was not reached versus 13.5 months, with a median PFS also significantly improved at about 14 months versus 4 months in the control. CRS of note in the glofitamab arm was mostly grade 1 or 2, with only about 2.3% grade 3 events. And three of the four patients had grade 1 or 2 neurotoxicity. So, John, putting this into context, I think it's encouraging that we now have randomized data showing the superiority of a bispecific plus chemotherapy over rituximab plus chemotherapy in transplant-ineligible patients. And while only 8% of the patients in the STARGLO study had prior anti-CD19 CAR T-cell therapy, I think this regimen could be considered in those patients who are ineligible for transplant or CAR T-cell therapy. Dr. John Sweetenham: Yeah, I agree. I think a couple of other compelling numbers to me were the fact that around 55% of these patients were alive at 2 years in the group who'd received glofitamab, and that almost 90% of those having that arm of the study who had a CR at the end of treatment were alive at 12 months. So, clearly, it's an active agent and also a kind of great off-the-shelf fixed-duration alternative in these relapsed and refractory patients. Dr. Marc Braunstein: I agree, and I would also note that the phase 3 SKYGLO study is looking at glofitamab plus Pola-R-CHP versus Pola-R-CHP alone. So, we may even be using these eventually in the first-line setting. Dr. John Sweetenham: Absolutely. Let's stay on the theme of diffuse large B-cell lymphoma and look at one other abstract in that space, which was Abstract 7000. This was a study from the HOVON group in the Netherlands, which looked at the prospective validation of end-of-treatment circulating tumor DNA in the context of a national randomized trial. What are your thoughts on this? Dr. Marc Braunstein: So, non-invasive liquid biopsies to detect and monitor cancers via circulating tumor-derived DNA or ctDNA, you know, is really emerging as a valuable tool in both solid and liquid tumors to understand disease biology, and also for drug development. So, to date, the most established application of ctDNA in lymphoma, I would say, is really for monitoring of minimal residual disease. So, in this correlative study by Steven Wang and colleagues in the HOVON group, they evaluated the prognostic significance of MRD status as assessed by ctDNA following first-line treatment with curative intent with either R-CHOP or dose-adjusted R-EPOCH. At the end of treatment, encouragingly, 76% of patients were MRD-negative, and 24% were MRD-positive. Now, of note, MRD-positive status at the end of treatment predicted inferior progression-free survival at 2 years, with only 28% of patients who are MRD-positive being progression-free versus 88% who are MRD-negative. And in fact, all the patients who failed to achieve a complete response after first-line treatment and were MRD-positive ultimately relapsed. So, circulating tumor cells are rarely found in large B-cell lymphomas, and so this study really builds on accumulating data that ctDNA has clinical value to detect residual disease with a non-invasive approach. So, there are many implications of how we could potentially use this to detect early signs of relapse, to potentially escalate treatment for consolidation if patients remain MRD-positive. So, I think this will eventually become utilized in clinical practice. Dr. John Sweetenham: Yeah, I agree. I think it's interesting that it provided an independent assessment of response, which was independent, in fact, of the results of PET-CT scanning and so on, which I think was very interesting to me. And the authors of the abstract actually commented in their presentation that they think this should be integrated as part of the standard response assessment now for patients with large B-cell lymphoma. Would you agree with that? Dr. Marc Braunstein: I would. For one thing, it allows repeated sampling. It's a non-invasive approach; it doesn't necessarily require a bone marrow biopsy, and it may have more sensitivity than conventional response measures. So, I think having a standardized system to assess ctDNA will be helpful, and definitely, I think this will be a valuable biomarker of disease response. Dr. John Sweetenham: Okay, great. Thanks. We're going to change gear again now, and we're going to highlight two abstracts in the multiple myeloma space. The first one of these is Abstract 7507. And this abstract reported on the long-term results of the CARTITUDE study for patients with relapsed and refractory multiple myeloma. What are your comments on this presentation? Dr. Marc Braunstein: So, this study actually got a lot of press, and I've already had multiple patients asking me about CAR T-cells as a result. Just as some background, CAR T-cells targeting BCMA, which is pretty much universally expressed on malignant plasma cells in myeloma, have really shown remarkable responses, especially in heavily pretreated patients, showing superior progression-free survival in both later and earlier phases of the disease, including in randomized studies in patients with second-line or beyond. So, the CARTITUDE-1 was really the original Phase 1/2 study of ciltacabtagene autoleucel, one of the two approved anti-BCMA CAR T-cell products, which was investigated in patients with a median of six to seven prior lines of therapy. So, these were patients who were pretty heavily pretreated. So, in the study presented by Voorhees at this year's ASCO meeting, this was the long-term follow-up at a median of 5 years from the one-time CAR infusion in these patients with a median of five prior lines of therapy. And remarkably, of the 97 patients, 33% remained progression-free at 5 years plus, without needing any further myeloma treatment during that time. And among those 33% of patients, 23% had high-risk cytogenetics, which we know are notoriously difficult to achieve responses in. What was interesting that they presented as correlative studies was there were some biomarkers that were distinguishing the patients who had the long PFS, including enrichment of more naive T-cells in the product, lower neutrophil-to-T-cell ratio, higher hemoglobin and platelets at baseline, and higher CAR T-cell levels relative to soluble BCMA levels. And the fact that they reported a median overall survival of 61 months in these really heavily pretreated patients, I think these data are impressive. I think we're going to continue to be using CAR T even earlier in the disease status than fifth or sixth line, as it was studied in CARTITUDE-1. There are even ongoing studies looking at first-line treatment with CAR T-cells. Dr. John Sweetenham: So, do you think that those 33% of patients who are disease-free at 5 years, do you think any of those are cured?  Dr. Marc Braunstein: That was one of the headlines in the press. I think if we're going to discuss things like "operational cures," where we're transforming myeloma into really a chronic disease, where patients can live practically a normal life expectancy, I think the measure of 5 years, especially in this population that was explored in CARTITUDE-1, I think we can call that close to a cure. Dr. John Sweetenham: Okay. Well, thank you. Exciting data, for sure. We're going to conclude today with another abstract in the multiple myeloma space. And this was Abstract 7500, which looked at an MRD, minimal residual disease-driven strategy following induction and transplant-eligible newly diagnosed multiple myeloma patients and reported on the primary endpoints of the phase 3 MIDAS trial. Can you walk us through this one, Marc? Dr. Marc Braunstein: Absolutely. It is a bit more complicated than the prior one we discussed because this is a randomized study with four arms. So, I'll start by saying that anti-CD38-based quadruplet regimens continue to show superior outcomes in both transplant-eligible and -ineligible newly diagnosed multiple myeloma patients. The MIDAS study mentioned is an open-label phase 3 trial with four arms in transplant-eligible newly diagnosed myeloma patients.  And initially, these patients were all treated with quadruplet therapy with the anti-CD38 antibody isatuximab combined with carfilzomib, lenalidomide, and dexamethasone in 718 newly diagnosed myeloma patients. So, they received the quadruplet regimen for six cycles and then were randomized based on their MRD status at 10 to the negative fifth following six cycles of induction. And that first randomization, if they were MRD-negative, was to either consolidation with six more cycles of the quadruplet regimen or transplant, autologous transplant, plus two cycles additionally of the quadruplet regimen. And both arms were followed by lenalidomide maintenance. The primary endpoint was MRD negativity at 10 to the negative sixth prior to entering the lenalidomide maintenance component. And in addition, the patients who were MRD-positive after induction were randomized to transplant plus two cycles of consolidation or a tandem autologous transplant. So, the median follow-up of the study was about 16 months, and the pre-maintenance rate of MRD negativity was high, between 84 to 86% between the two arms who were MRD-negative, which was not significantly different. And as far as the 233 patients who were MRD-positive, the pre-maintenance MRD negativity was also not significantly different at 40% for those who received autologous transplant, and 32% who received a tandem transplant. So, there's a lot of debate in the myeloma field about the evolving role of autologous transplant and whether transplant still plays a significant role in patients who are either MRD-negative after induction or who have deep remissions and are of standard risk. So, I think these data suggest that patients who are MRD-negative after induction with a quadruplet regimen studied here, which was Isa-KRd, plus consolidation, may possibly be able to forego consolidation with autologous transplant. And likewise, for those patients who are MRD-positive after induction, tandem transplant didn't seem to provide much of a benefit compared to single transplant, which is consistent with prior studies such as the StaMINA study. Dr. John Sweetenham: So, where do you think this leaves us, Marc? Are we going to need more studies before we have any definitive guidance on whether an autologous transplant is still appropriate for those patients who are MRD-negative? Dr. Marc Braunstein: Well, as clinicians, we want to do what's best for our patient. And in myeloma, the best we can do is to get as deep remissions as possible, meaning MRD negativity. And so, I think it's clear from the MIDAS study and others that quadruplet regimens provide the deepest remissions when given upfront. We can debate the role of autologous transplant. I think certainly the role of tandem autologous transplant is fading. But as far as a single autologous transplant as consolidation, I think it's reasonable as a goal to try to achieve MRD negativity after the transplant, especially for patients who remain MRD-positive after induction. Dr. John Sweetenham: Okay, great. Marc, thanks as always for sharing your insights on the heme malignancies studies from the ASCO meeting this year and for joining us on the ASCO Daily News Podcast. Always appreciate hearing your thoughtful and balanced input on these. Dr. Marc Braunstein: My pleasure. Thank you, John. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's guest:  Dr. John Sweetenham Dr. Marc Braunstein   @docbraunstein     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:  Dr. John Sweetenham:  Consulting or Advisory Role: EMA Wellness  Dr. Marc Braunstein:  Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp  Speakers' Bureau: Janssen Oncology  Research Funding (Institution): Janssen, Celgene/BMS

The Community Relations Service was created by the Civil Rights Act to smooth out race relations during desegregation, but like every government agency, it quickly took on a life of its own. The shadowy organization has an incredible level of secrecy and pushes woke agendas, including the normalization of trans kids and the planting of mosques in all Christian towns. Worst of all, the CRS is known to compel grieving families who are the victims of minority crime to deliver prepared statements downplaying the violence of their attackers. Academic Agent joins me to discuss.  Follow on: Apple: https://podcasts.apple.com/us/podcast/the-auron-macintyre-show/id1657770114 Spotify: https://open.spotify.com/show/3S6z4LBs8Fi7COupy7YYuM?si=4d9662cb34d148af Substack: https://auronmacintyre.substack.com/ Twitter: https://twitter.com/AuronMacintyre Gab: https://gab.com/AuronMacIntyre YouTube:https://www.youtube.com/c/AuronMacIntyre Rumble: https://rumble.com/c/c-390155 Odysee: https://odysee.com/@AuronMacIntyre:f Instagram: https://www.instagram.com/auronmacintyre/ Learn more about your ad choices. Visit megaphone.fm/adchoices

Chronic sinusitis might be doing more than just clogging your nose–it could be clouding your brain. In this episode of Backtable ENT, Dr. Aria Jafari, an assistant professor at the University of Washington and co-director of the Neuroendocrinology Advanced Sinus and Skull-base Surgery Fellowship, discusses the connection between sinusitis and cognitive dysfunction with hosts Dr. Gopi Shah and Dr. Ashley Agan. --- SYNPOSIS Dr. Jafari shares how his interest in this field developed and details his research on the relationship between chronic rhinosinusitis (CRS) and brain function. The conversation highlights the comprehensive impact of sinus inflammation on overall health, emphasizing the importance of viewing CRS as a whole-body condition. They also discuss patient experiences, the methodologies used to assess cognitive dysfunction, potential treatments, and what's next in the research frontier.---TIMESTAMPS00:00 - Introduction 06:18 - The Impact of CRS on Quality of Life14:02 - Understanding Brain Fog and Cognitive Dysfunction24:29 - Pathophysiology and Theories of Cognitive Dysfunction27:44 - Chronic Inflammation and Cognitive Effects28:59 - Impact of Biologics on Cognitive Function31:28 - Risk Factors for Cognitive Dysfunction35:02 - Olfactory Symptoms 37:13 - Future Research and Treatment Approaches45:31 - Conclusion and Final Thoughts --- RESOURCES Dr. Aria Jafari https://www.uwmedicine.org/bios/aria-jafari

Kent Redding's path from retail mogul to real estate powerhouse isn't what you'd expect - especially when leadership, empathy, and branding collide. In this episode, Kent shares the surprising lessons he learned that still shape his business today. You'll walk away rethinking what it really means to build trust, show up, and lead with heart. Plus, don't miss the story of the open house that literally caused a traffic jam.   Key takeaways to listen for How Kent turned personal values into a business branding strategy that stuck What managing 400 retail employees teaches you about long-term client loyalty The marketing wisdom that still drives Kent's success today Reasons self-awareness and empathy matter more than market trends Is volunteering with your local REALTOR® association a great career move?   About Kent ReddingKent is a top-producing REALTOR®, 2024 President of the Austin Board of REALTORS®, and a 20-year veteran with Berkshire Hathaway. Known for his client-first approach, Kent combines entrepreneurial grit with a deep commitment to the community. He's a ten-time Platinum Top 50 award winner and holds designations including GRI, CRS, ABR, ePro, MRP, and CLHMS. Outside of real estate, Kent volunteers with groups like Community First! Village, Hungry Souls, and Red Oak Hope.   Connect with Kent Website: Kent Redding Facebook: Kent Redding | Kent Redding Team Instagram: @kentreddinggroup LinkedIn: Kent Redding Email: kent@callkent.com Contact Number: (512) 797-5737   Connect with LeighPlease subscribe to this podcast on your favorite podcast app at https://pod.link/1153262163, and never miss a beat from Leigh by visiting https://leighbrown.com. DM Leigh Brown on Instagram @ LeighThomasBrown.   Sponsors"You Ask. Leigh Answers." Your Affordable Coaching ProgramHey there, real estate pros! Are you ready for some more Leigh Brown wisdom in your life? Then don't miss out on my brand-new program, "You Ask. Leigh Answers." It's your exclusive gateway to the insights and advice you need to supercharge your real estate business. With "You Ask. Leigh Answers." you get Direct Access to Leigh Brown, directly! Expert Coaching, Community Connection, and Extensive Resources. Whether listening to this on the go or watching at home, sign up today at Answers.RealEstate and take your business to the next level. Trust me, you'll be glad you did!