Podcasts about revlimid

ProPublica reporter David Armstrong began investigating the pharmaceutical industry when he learned a single pill of his cancer treatment costs about the same as a new iPhone — but costs 25 cents to make. His investigation into the discovery and marketing of the drug Revlimid revealed strategies employed by pharmaceutical companies to ward off competition, and keep prices of their medications high. We'll also talk about ways insurance companies deny claims for tests and treatment recommended by doctors.Also, David Bianculli reviews a music documentary about singer-songwriter Janis Ian.Learn more about sponsor message choices: podcastchoices.com/adchoicesNPR Privacy Policy

ProPublica reporter David Armstrong began investigating the pharmaceutical industry when he learned a single pill of his cancer treatment costs about the same as a new iPhone — but costs 25 cents to make. His investigation into the discovery and marketing of the drug Revlimid revealed strategies employed by pharmaceutical companies to ward off competition, and keep prices of their medications high. We'll also talk about ways insurance companies deny claims for tests and treatment recommended by doctors.Also, David Bianculli reviews a music documentary about singer-songwriter Janis Ian.Learn more about sponsor message choices: podcastchoices.com/adchoicesNPR Privacy Policy

In this episode of Targeted Talks, Alfred L. Garfall, MD, discusses the phase 2 BMT CTN 1902 trial (NCT05032820) of idecabtagene vicleucel (ide-cel; Abecma), a study focused on patients with multiple myeloma who had a suboptimal response to first-line therapy, including autologous hematopoietic cell transplant and lenalidomide (Revlimid) maintenance.

Episode 184: Multiple Myeloma BasicsSub-Interns and future Drs. Di Tran and Jessica Avila explain the symptoms, work up and treatment of multiple myeloma. Written by Di Tran, MSIV, Ross University School of Medicine; Xiyuan Yang, MSIV, American University of the Caribbean. Comments by Jessica Avila, MSIV, American University of the Caribbean. Edits by Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Di: Hi everyone, this is Di Tran, 4th year medical student from Ross university.  It's a pleasure to be back.  To be honest, this project is a part of teamwork of two medical students, myself and another 4th year, her name is XiYuan.  She came from the AUC. Unfortunately, due to personal matters she was unable to make it to the recording today which makes me feel really sad. Jessica: My name is Jessica Avila, MSIV, American University of the Caribbean.Di: The topic we will present today is Multiple Myeloma. Multiple myeloma is typically a rare disease and it's actually a type of blood cancer that affects plasma cells in the bone marrow.Jessica: Let's start with a case: A 66-year-old male comes to his family doctor for an annual health checkup. He is not in any acute distress but he reports that he has been feeling tired and weaker than usual for the last 3 months. He also noticed that he tends to bruise easily. He has a history of arthritis and chronic joint pain, but he thinks his back pain has gotten worse in the last couple of months. Upon checking his lab values, his family doctor found that he has a calcium level of 10.8 and a creatinine level of 1.2, which has increased from his baseline. Given all that information, what do you think his family doctor is suspecting? And what kind of tests she can order for further evaluation?Di: Those symptoms sound awfully familiar – are we talking about the CRAB? You know, the diagnostic criteria for Multiple Myeloma.Jessica: Exactly! Those are called “myeloma-defining events.” Do you remember what those are?Di: CRAB criteria comes in 4 flavors.  It's HYPERCALCEMIA with >1mg/dL, RENAL INSUFFICIENCY with serum creatinine >2mg/dL, ANEMIA with hemoglobin value 10% plasma cells, PLUS any one or more of the CRAB features, we can make the official diagnosis of multiple myeloma. Di:  Before we go deeper, let's back up a little bit and do a little background.  So, what do we know about the immunoglobulins, also known as antibodies? Back from years of studying from medical school, we know that the plasma cells are the ones that producing the antibodies that help fight infections.  There  are various kinds that come with various functions.  Each antibody is made up of 2 heavy chains and 2 light chains.  For heavy chains, we have A, D, E, G, M and for light chains we have Kappa and Lambda.Jessica: Usually, the 5 possible types of immunoglobulins for heavy chains would be written as IgG, IgA, IgD, IgE, and IgM.  And the most common type in the bloodstream is nonetheless the IgG. Di: What is multiple myeloma? In myeloma, all the abnormal plasma cells make the same type of antibody, the monoclonal antibody.  The cause of myeloma is unknown, but there are lots of studies and evidence that show a number of potential etiologies, including viral, genetic, and exposure to toxic chemicals, especially the Agent Orange, which is a chemical used as herbicide and defoliant. It was used as a chemical warfare by the U.S. military during the Vietnam War from 1961 to 1971.Jessica: We need to order some specific blood tests to see if there is elevated monoclonal proteins in the blood or urine. So, to begin with we'll need to take a very thorough history and physical exam. Next, we'll do labs, such as CBC, basic metabolic panel, calcium, serum beta-2 microglobulin, LDH, total protein, and some not so common tests: serum protein electrophoresis (SPEP), immunofixation of blood or urine (IFE), quantitative immunoglobulins (QIg), serum free light chain assay, and serum heavy/light chain ratio assay.If any of the results is abnormal, we should consider referring our patient to an oncologist.Di: Interesting! I read that Multiple Myeloma symptoms vary in different patients.  In fact, about 10-20% of patients with newly diagnosed myeloma do not have any symptoms at all.   Otherwise, classic symptomatic presentations are weakness, fatigue, increased bruising under the skin, reduced urine output, weakened bones that is likely prone to fractures, etc. And if multiple myeloma is highly suspected, a Bone Marrow biopsy should be done with testing for flow cytometry and fluorescent in situ hybridization (FISH). Actually, if any of the “Biomarkers of malignancy (SLIM)” is met we can also diagnose multiple myeloma even without the CRAB criteria. Jessica: The diagnosis is made if one or more of the following is found: >= 60% of clonal plasma cells on bone marrow biopsy, > 1 lytic bone lesion on MRI that is at least 5mm in size, or a biopsy confirmed plasmacytoma. Di: Imaging comes in at the final step especially if we able to find one or more sites of osteolytic bone destruction > 5mm on an MRI scan.Jessica: What if the bone marrow biopsy returns > 10% of monoclonal plasma cells, but our patient doesn't have either the CRAB or the Biomarker criteria? Di: That's actually a very good question, since Multiple Myeloma is part of a spectrum of plasma cell disorders. That's when smoldering myeloma comes into play. It is a precursor of active multiple myeloma. Smoldering myeloma is further categorized as high-risk or low-risk based on specific criteria.A less severe form is called Monoclonal Gammopathy of Undetermined Significance, or simply MGUS, with < 10% bone marrow involvement. Those are diagnoses we give once we rule out actual multiple myeloma, which are defined by the amount of M-protein in the serum.Jessica:  When to get started on treatment? Multiple Myeloma is on a spectrum of plasma cells proliferative disorders, starting from MGUS to Smoldering Myeloma, to Multiple Myeloma and to  Plasma Cell Leukemia.  Close supervision/active watching is enough for MGUS and low risk Smoldering Myeloma. But once it has progressed to high-risk smoldering myeloma or to active Multiple Myeloma, chemotherapy is usually required. Some situations may require emergent treatment to improve renal function, reduce hypercalcemia, and to prevent potential infections.Di: As of 2024, treatment of Multiple Myeloma comprises the Standard-of-Care approved by the FDA. In fact, the quadruple therapy is a combination of 4 different class of drugs that include a monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug, and a steroid. Jessica: They are Darzalex (daratumumab), Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone.  Other treatment plans for Multiple Myeloma include chemotherapy, immunotherapy, radiation therapy (for plasmacytomas) and stem cell transplants. The patient will also be on prophylaxis acyclovir and Bactrim while on chemotherapy. Sometimes anticoagulants are also considered because the chemo increases the risk of venous thromboembolic events.Di: Although the disease is incurable, but with the advancing of novel therapies and clinical trials patients with multiple myeloma are able to live longer.  Problem is the majority of patients diagnosed with Multiple Myeloma are older adults (>65), the risk of falling is adding to multiple complications of the disease itself, such as bone density loss, pain, neurological compromises, distress and weakness.  Palliative care may come in help at any point in time throughout the course of treatment but is most often needed at the very end of the course. Jessica, can you give us a conclusion for this episode?Jessica: Multiple Myeloma may not be the most common cancer, but we have to be aware of the symptoms and keep it in our differential diagnosis for patients with bone pain, easy bruising, persistent severe headaches, unexplained renal dysfunction, and remember the CRAB: HyperCalcemia, Renal impairment, Anemia and Bone lesions.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:International Myeloma Foundation. (n.d.). International Myeloma Working Group (IMWG) criteria for the diagnosis of multiple myeloma. https://www.myeloma.org/international-myeloma-working-group-imwg-criteria-diagnosis-multiple-myeloma Laubach, J. P. (2024, August 28). Patient education: Multiple myeloma symptoms, diagnosis, and staging (Beyond the Basics). UpToDate. https://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics.University of California San Francisco. (n.d.). About multiple myeloma. UCSF Helen Diller Family Comprehensive Cancer Center. https://cancer.ucsf.edu/research/multiple-myeloma/about Theme song, Works All The Time by Dominik Schwarzer, YouTube ID: CUBDNERZU8HXUHBS, purchased from https://www.premiumbeat.com/.

(Disclaimer: This episode contains advice on nutrition and lifestyle. Always consult your health care team regarding your personal circumstances).In this episode, we speak with Terena from Tampa, Florida, about her journey with CAR T-cell therapy, covering her experiences from diagnosis through recovery and remission. Diagnosed with mantle cell lymphoma, a type of non-Hodgkin's lymphoma, in September 2019, Terena endured years of misdiagnosis as her initial symptoms, such as severe hot flashes and night sweats, were attributed to menopause. It wasn't until a bone marrow biopsy that she was correctly diagnosed.Following her diagnosis, Terena underwent extensive testing, including specialized genetic tests like FoundationOne Heme and clonoSEQ, which helped tailor her treatment plan. She started on a combination therapy of Revlimid and rituximab before transitioning to CAR T-cell therapy in December 2020. She shares how the preparation for CAR T involved rigorous health screenings, including mental health assessments and apheresis, to collect her T cells.Terena details the intensive hospital stay during CAR T, where she faced several challenging side effects like cytokine release syndrome, neurotoxicity, and significant weight loss due to radiation-induced nausea. Despite these challenges, she avoided some severe complications such as seizures or viral reactivations, thanks to preemptive treatments and vigilant care. Her remission came three months post-treatment, a milestone that was both a relief and a testament to the effectiveness of the therapy.The cost of CAR T therapy was staggering, with an itemized hospital bill exceeding a million dollars. Fortunately, her insurance (including Medicare) covered a significant portion, though she emphasizes the importance of being financially prepared for such high medical expenses.Post-remission, Terena has made significant lifestyle changes to support her health. She follows a strict anti-inflammatory diet, avoiding GMOs, processed foods, and conventional dairy and meat products. She shares her regimen of juicing, incorporating nutrient-rich foods like organic berries, avocados, and cruciferous vegetables. Additionally, she has overhauled her home environment, switching to non-toxic cleaning products and cosmetics, using water and air filters, and incorporating wellness practices like infrared sauna therapy and regular exercise.Terena's commitment to reducing environmental toxins extends to every aspect of her life. She no longer uses products with harmful chemicals, such as nail polish or hair dye, and relies on digital tools to evaluate the safety of her food and personal care products. Her integrative health approach, combining conventional and holistic practices, plays a crucial role in maintaining her well-being.Her story is not only about overcoming physical challenges but also about the emotional and logistical aspects of undergoing such intensive treatment. From pre-paying bills and preparing meals in advance to relying on friends and family for transportation during her recovery, Terena's experience highlights the need for a strong support system. Her openness and detailed sharing of her journey are bound to help others navigating similar paths.Links: Gluten Free Scanner App: https://glutenfreescanner.app/EWG's "Clean Fifteen" List: https://www.ewg.org/foodnews/clean-fifteen.phpEWG's "Dirty Dozen" List: https://www.ewg.org/foodnews/full-list.phpFoundationOne Heme - foundationmedicine.comclonoSEQ - clonoseq.comThis season is made possible thanks to our sponsors:Kite, a Gilead company: http://www.kitepharma.com/and Bristol Myers Squibb's CAR T support services program:https://www.celltherapy360.com/ Follow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/Or visit our website at https://www.nbmtlink.org/

CancerNetwork® spoke with James R. Berenson, MD, about the potential role that JAK inhibitors may play in the treatment of patients with multiple myeloma. The conversation focused on the rationale for researching this drug class as well as ongoing initiatives to assess the utility of agents like ruxolitinib (Jakafi) for this patient population. Berenson, founder, medical and scientific director, and president and chief executive officer of the Institute for Myeloma and Bone Cancer Research and private practitioner in West Hollywood, California, described the factors associated with the overexpression of JAK in the bone marrow, which may constitute a prime survival factor for multiple myeloma. This overexpression may affect the checkpoint inhibitor proteins in the body, resulting in resistance to standard anti-myeloma therapies such as immunomodulatory drugs.  Additionally, he mentioned a patient case that had involved a scenario in which JAK-mutated multiple myeloma progressed following prior treatment with lenalidomide (Revlimid). According to Berenson, the disease's resistance to lenalidomide was primarily associated with proteins driven by JAK; subsequent treatment involving JAK inhibition proved successful in restoring the efficacy of lenalidomide.  Based on a rationale to target JAK overactivity in the bone marrow and results from this patient case, Berenson and colleagues have focused on researching ruxolitinib as a therapeutic candidate for potentially improving outcomes in multiple myeloma via JAK inhibition. Findings from a phase 1 trial (NCT03110822), for example, have demonstrated that the efficacy and tolerability of ruxolitinib plus methylprednisolone can be extended with lenalidomide in those with multiple myeloma. Additionally, other ongoing trials aim to combine ruxolitinib with agents such as selinexor (Xpovio). “The question is, where will ruxolitinib sit in the sequencing of treatment of [patients with] multiple myeloma? Where will selinexor be?” Berenson stated. “At this point, there's certainly been low use of these drugs, especially ruxolitinib in multiple myeloma. We hope, with a more positive signal, these drugs will move further up in the algorithm of how you treat multiple myeloma.” Reference Berenson JR, Limon A, Rice S, et al. A phase I trial evaluating the addition of lenalidomide to patients with relapsed/refractory multiple myeloma progressing on ruxolitinib and methylprednisolone. Target Oncol. 2024;19(3):343-357. doi:10.1007/s11523-024-01049-w

During the 2024 Oncology Nursing Society Congress, CancerNetwork® spoke with multiple registered nurses about research they presented on safely administering treatment options such as CAR T-cell therapy and bispecific T-cell engager (BiTE) therapy in patients with multiple myeloma and other malignancies. Ishmael Applewhite, BSN, RN-BC, OCN, a registered nurse at the University of Rochester Medical Center, highlighted the management of adverse effects including peripheral neuropathy in patients with multiple myeloma undergoing treatment with ciltacabtagene autoleucel (cilta-cel; Carvykti). He discussed these treatment strategies in the context of a presentation he gave on findings from the phase 3 CARDITUDE-4 trial (NCT04181827), in which investigators assessed treatment with cilta-cel in those who were refractory to lenalidomide (Revlimid).1 According to Applewhite, cilta-cel may offer “another path” aside from standard treatment options such as chemotherapy and give “more time” to patients with multiple myeloma. Additionally, Leslie Bennett, MSN, RN, a nurse coordinator at Stanford Healthcare, highlighted the importance of identifying and mitigating cranial nerve palsy (CNP) in patients with multiple myeloma who are treated with cilta-cel. At the conference, Bennett presented data on CNP outcomes across various studies, which included the phase 1/2 CARTITUDE-1 trial (NCT03548207), phase 2 CARTITUDE-2 trial (NCT04133636), and phase 3 CARTITUDE-4 trial (NCT04181827).2 According to findings from this presentation, patients had CNP onset at a median of approximately 3 weeks after beginning treatment with cilta-cel. Most cases of CNP tended to occur in male patients. Kathy Mooney, MSN, RN, ACNS-BC, BMTCN®, OCN®,clinical program director at Johns Hopkins Hospital and Johns Hopkins Health System, spoke about a study designed to evaluate the feasibility and safety of using BiTE therapy to treat those with cancer in an outpatient setting.3 Mooney emphasized multidisciplinary collaboration among nurses, pharmacy providers, and social workers as part of monitoring patients for toxicity as they undergo treatment with BiTE agents. References 1.        Applewhite I, Elfrink G, Esselmann J, Lonardi C, Florendo E, Sidiqi MH. Efficacy and adverse events after ciltacabtagene autoleucel treatment in the CARTITUDE-4 as-treated population consisting of patients with lenalidomide-refractory multiple myeloma who received 1-3 prior lines of therapy. Presented at: 2024 Oncology Nursing Society Congress; April 24-28, 2024; Washington, DC. 2.        Bennett L, Kruyswijk S, Sidana S, et al. Incidence and management of cranial nerve impairments in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies. Presented at: 2024 Oncology Nursing Society Congress; April 24-28, 2024; Washington, DC. 3.        Mooney K, Allen N, Anderson K, Zukas A. Taking a BiTE out of hospital admission days using a team approach to managing patients at risk for treatment related toxicities. Presented at: 2024 Oncology Nursing Society Congress; April 24-28, 2024; Washington, DC.   

Foundations of OncoPharm episode on lenalidomide (Revlimid) and its MOA, use, dosing, & toxicity.

In this episode of "The Top Line," we delve into the uncharted territory that pharma marketers face, from harnessing AI's potential to navigating the Inflation Reduction Act. Ayla Ellison, editor-in-chief of Fierce Life Sciences and Healthcare, engages with three industry experts to unravel the opportunities and challenges that lie ahead. In the first segment, Robert Allen, the leader behind engagement and channel planning for U.S. Oncology at Bristol Myers Squibb, shares his insights into strategic planning for customer engagement and channel strategies. Next, Terry Terifay, the Chief Commercial Officer at Azurity Pharmaceuticals, offers a glimpse into what the future holds for the industry. In the third segment, Dorothy Gemmel, the Chief Commercial Officer of GoodRx, shares the projects she's excited about and her biggest piece of advice for others in the industry." To learn more about the topics in this episode:  Will Big Pharma engage in Medicare price negotiations? Merck, AZ and BMS say they will Providers can now see patients' insurance coverage in GoodRx's cost comparison tool Bristol Myers banks on 25-plus label expansions to help weather IRA, Revlimid generics and more GoodRx, Walgreens team to lower prices for 200 drugs Fierce Pharma unveils the winners of the 5th annual creativity contest for outstanding marketing campaigns See omnystudio.com/listener for privacy information.

As part of a CancerNetwork® Frontline Forum program, Joselle Cook, MBBS; Matthew James Pianko, MD; Luciano Costa, MD, PhD; and Timothy Schmidt, MD, reviewed key data updates and real-world practice findings in newly diagnosed multiple myeloma (NDMM), and how they may impact patient subgroups including those with transplant-ineligible NDMM. Cook, a hematologist specializing in the management of patients with multiple myeloma at the Mayo Clinic in Rochester, Minnesota; and Pianko, a hematologist in the Division of Hematology and Oncology at The University of Michigan-Ann Arbor, led one part of the discussion. They discussed efficacy results from studies including the phase 3 MAIA study (NCT02252172), which assessed daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone vs lenalidomide plus dexamethasone in previously untreated multiple myeloma. They also spoke about the selection of patients with transplant ineligible multiple myeloma for triplet vs doublet induction therapy regimens and potential disparities in care for patients of racial and ethnic minorities. “We need trials to accommodate patients who are working [and patients] who are unpartnered, [and] we need to do more to understand the biologic drivers [of multiple myeloma] in Black patients,” Cook said. “Even though we have this explosion of [new] therapies onto the scene, we still have so much to do to make access to these novel treatments accessible and more equitable for everyone.” Costa, a professor of Medicine and director of the Multiple Myeloma Program at The University of Alabama at Birmingham, and Schmidt, assistant professor in the Division of Hematology, Medical Oncology, and Palliative Care within the Division of Medicine at The University of Wisconsin, also discussed updates in the multiple myeloma space, which included a review of findings from the phase 2 GRIFFIN trial (NCT02874742). In this trial, investigators assessed daratumumab plus lenalidomide, bortezomib (Velcade), and dexamethasone as a treatment for patients with transplant-ineligible NDMM. Costa and Schmidt also spoke about approaching consolidation and maintenance therapy for patients with transplant-ineligible NDMM. “As we're trying to move treatments into earlier lines of therapy—particularly things like bispecifics and CAR T—improving access is [something] that we as a field and as a community need to address,” Schmidt said.  Don't forget to subscribe to the “Oncology On-The-Go” podcast on Apple Podcasts, Spotify, or anywhere podcasts are available.

In a Twitter Spaces edition of the Oncology-On-The-Go podcast, Rafael Fonseca, MD and Krina Patel, MD, MSc spoke with CancerNetwork® about how key findings from multiple myeloma trials presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meetingmay impact the treatment paradigm.  Fonseca, director of Innovation and Transformation Relationships at the Mayo Clinic in Phoenix, Arizona and Patel, an associate professor in the Department of Lymphoma/Myeloma in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, detailed results from the phase 1b RedirecTT-1 trial (NCT04586426) assessing teclistamab-cqyv (Tecvayli) plus talquetamab in those with relapsed/refractory multiple myeloma. In the RedirectTT-1 trial, investigators reported an objective response rate (ORR) of 86.6% across all dose levels and 96.3% at the recommended phase 2 dose. Additionally, the combined complete response (CR) or stringent CR rate was 40.2% and 40.7% at each respective dose level. Another trial of interest that Fonseca and Patel discussed included the phase 2 LINKER-MM1 trial (NCT03761108), evaluating linvoseltamab (REGN5458) in relapsed/refractory multiple myeloma. In the study, the agent elicited an ORR of 71% at the 200 mg dose level. Moreover, the CR rate was 14%, the very good partial response (PR) rate was 29%, and the PR rate was 12%. The estimated 6-month progression-free survival (PFS) rate among patients receiving the regimen was 72.7%. Fonseca and Patel also discussed results from the phase 3 CARTITUDE-4 trial (NCT04181827), comparing ciltacabtagene autoleucel (cilta-cel; Carvykti) with standard of care in lenalidomide (Revlimid)-refractory multiple myeloma. In patients receiving cilta-cel, the median PFS was not reached (NR, 95% CI, 22.8 months-not estimable [NE]) vs 11.8 months (95% CI, 9.7-13.8) among those receiving standard of care. The 12-month PFS rate in each respective arm was 76% vs 49%. Don't forget to subscribe to the “Oncology On-The-Go” podcast on Apple Podcasts, Spotify, or anywhere podcasts are available.

Maintenance therapy over the past several years has commonly included the use of Revlimid (lenalidomide) over a long period of time. Is more better? Does more maintenance therapy or certain combinations help extend remissions or help patients deepen their responses?  Ashraf Badros, MD, of the University of Maryland will join the HealthTree Podcast for Multiple Myeloma to talk with us about the rationale behind the AURIGA clinical trial using daratumumab and lenalidomide following stem cell transplant for patients who are still MRD positive.  Myeloma experts are working to identify more personalized approaches for each type of myeloma patient. We know that patients who are still MRD positive following high dose therapy are more likely to have shorter remissions and the use of a different maintenance therapy may help patients who aren't getting their deepest responses do better over time.  Thanks to our episode sponsor, Takeda Oncology

Maintenance therapy over the past several years has commonly included the use of Revlimid (lenalidomide) over a long period of time. Is more better? Does more maintenance therapy or certain combinations help extend remissions or help patients deepen their responses?  Ashraf Badros, MD, of the University of Maryland will join the HealthTree Podcast for Multiple Myeloma to talk with us about the rationale behind the AURIGA clinical trial using daratumumab and lenalidomide following stem cell transplant for patients who are still MRD positive.  Myeloma experts are working to identify more personalized approaches for each type of myeloma patient. We know that patients who are still MRD positive following high dose therapy are more likely to have shorter remissions and the use of a different maintenance therapy may help patients who aren't getting their deepest responses do better over time.  Thanks to our episode sponsor, Takeda Oncology

Biogen has been battling for a while now over Aduhelm's controversial FDA approval and subsequent narrow Medicare coverage decision. And those struggles have resulted in a significant company reorganization, including the CEO, Michel Vounatsos. After a five-year term, he is stepping down, and a hunt for his replacement is already underway. Also under discussion is the Fierce newsroom's assessment of the most influential people in biopharma—from CEOs to entrepreneurs, scientists and regulatory experts. And the Fierce Madness drug naming championship is the buzz around the newsroom this week, with names that sound like they're straight out of a Harry Potter spell. To learn more about the topics in this episode: Biogen sends CEO to the exit, abandons Aduhelm sales team in $1B overhaul Next Biogen CEO's most-prized expertise? Dealmaking experience, investors say Biogen shoves Aduhelm to the side. It's time for lecanemab Most influential people in biopharma—the CEOs AbbVie's cystic fibrosis long-game doesn't pay off, as Galapagos med fails in triple combo As superstar Revlimid fades faster than expected, BMS trims $600M from its 2022 sales projection Abbott's COVID test sales reach all-time high—and maybe for the last time, the company says As COVID testing cools, Thermo Fisher's biopharma services, clinical research revenues heat up Hologic's M&A deals aim to pick up the torch from COVID testing sales Siemens nearly doubles diagnostics forecast for the year amid renewed COVID testing surge BD tightens up revenue guidance after completing Embecta diabetes spinoff Bancel has 'never been as busy' amid M&A talks as Moderna preps for life after COVID Unwelcome surprise for Vertex as FDA slaps hold on phase 1/2 diabetes cell therapy study FDA plays tooth fairy, awards clearance to VideaHealth's cavity-spotting AI Wherefore Tavneos? ChemoCentryx and the Brand Institute explain how the #FierceMadness winner got its name ChemoCentryx' Tavneos trounces BioMarin's Voxzogo to win #FierceMadness drug name tournament championship The Top Line is produced by senior multimedia producer Teresa Carey, with editor-in-chief Tracy Staton, managing editor Querida Anderson, senior editors Annalee Armstrong, Ben Adams, Conor Hale and Eric Sagonowsky. The sound engineer is Caleb Hodgson. The stories are by all our “Fierce” journalists. See omnystudio.com/listener for privacy information.

6. april 2022 Vi fortsetter å snakke om tilgang til behandling i podkasten, og denne gangen har vi med oss Stine Høibak-Nissen, spesialrådgiver i Kreftforeningen og Thomas Axelsen, seksjonssjef for samfunnspolitikk i Kreftforeningen. De forteller oss hvordan det er å være kreftpasient i Norge i dag og få vite at den behandlingen som kunne hjulpet deg, den kan du ikke få i det offentlige Norge. Det er mange slike pasienter, og Thomas og Stine forklarer hvordan den juridiske rettigheten hver enkelt pasient har til forsvarlig helsehjelp ikke blir ivaretatt av systemet vi har i dag. Vi snakker mye om Revlimid for å eksemplifisere hvor lang tid det kan ta før en behandling blir tilgjengelig, og dette tilfellet mener Kreftforeningen viser at det bør være en kontrollinstans med metodevurderingene som gjøres av Statens legemiddelverk. Nå tar podkasten påskeferie. Riktig god påske til alle våre lyttere!

Hear how Jay Mei, MD, PhD, went from his benchtop years at the NIH to a blockbuster launch at Celgene (think, Revlimid, after stints at Novartis and J&J along the way) – to spearhead the multi-asset juggernaut that is the oncology company, Antengene. From it's “license and build” beginnings, to the advent of in-house programs (15 assets in all) Antengene is poised to hit multiple oncology targets, from a small molecule ERK 1/2 inhibitor, to a bispecific for PD-L1/ 4-1BB. And did I mention they have a global license, and are expanding indications for XPOVIO? Give a listen…

Guest host, Dr. John Sweetenham, associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Dr. Syed Abutalib, medical director of the Hematologic Malignancies and Stem Cell Transplant Program at the Cancer Treatment Centers of America in Zion, Illinois, discuss advances in CAR T-cell therapy in the management of lymphoma, the toxicities associated with CAR T, and emerging bispecific antibodies for the treatment of lymphomas.   Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News podcast. I'm John Sweetenham, the associate director for Clinical Affairs at UT Southwestern Harold C. Simmons Comprehensive Cancer Center and guest host of the podcast. I'm delighted to welcome my friend, Dr. Syed Abutalib, the medical director of the Hematologic Malignancies and Stem Cell Transplant Program at the Cancer Treatment Centers of America in Zion, Illinois. He's also associate professor at the Rosalind Franklin University of Medicine and Science, and founder and co-editor of Advances in Cell and Gene Therapy. Today, we're going to be discussing some of the recent advances in the use of CAR T-cell therapy in the management of lymphoma. Our full disclosures are available in the show notes, and disclosures relating to all episodes of the podcast can be found in our transcripts at asco.org/podcasts. Syed, it's great to have you on the podcast today. Thanks for coming. Dr. Syed Abutalib: Thank you, John. It's my honor. Dr. Sweetenham: Syed, the emergence of CAR T-cell therapy is having a transformed impact on the treatment landscape for hematologic malignancies in general, and for lymphoma in particular, and I'd like to give our listeners a sense of where we're at with CAR T-cell lymphoma. Can you tell us a little about the FDA approved agents which are now being used for the management of patients with malignant lymphoma? Dr. Syed Abutalib:  Sure, so there are, at this time, about five agents that are approved based on mainly a phase 2 single arm study controlling them with the historical data from Scholar One in diffuse large B-cell lymphoma. They are axicabtagene ciloleucel. We'll be calling this axi-cel, which was approved after the data ZUMA-1 for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. In this group, there were diffuse large B-cell lymphoma NOS, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and transformed diffuse large B-cell lymphoma from follicular lymphoma. The next agent that was approved was--let's see if I can pronounce it. It's the most difficult name--tisagenlecleucel which is tisa-cel was based on the JULIET trial. This drug was approved again for the adult patients with a relapsed/refractory large B-cell lymphoma after two lines of systemic therapy for the same indications as patients in ZUMA-1 trial except tisa-cel is not approved for the primary mediastinal large B-cell lymphoma. The next agent is lisocabtagene maraleucel. We will call this liso-cel. This agent was approved after the pivotal trial TRANSCEND NHL 001. And the unique thing about this trial was also there were two patients with CNS lymphoma in this trial. And again, the indications were similar to the axi-cel indication. And the fourth indication is for axicaptagene lisoleucel based on the ZUMA-5 trial, which was FDA approved for adult patients with relapsed/refractory follicular lymphoma after two or more lines of systemic therapy. And the last agent that has been approved is based on the trial of ZUMA-2, which is brexucabtagene autoleucel, brexu-cel. And this is approved for adult patients with relapsed or refractory mantle cell lymphoma. Dr. John Sweetenham: Syed, thanks for providing that background. As you've shown, there are multiple agents which have been through early phase clinical trials. They've been applied to various subtypes of malignant lymphoma. And furthermore, they've been used at various stages in the treatment algorithm for these lymphomas, albeit mostly in the relapsed and refractory setting. We've all been waiting for some time to start to see data emerging from prospective randomized trials of CAR T-cell therapy versus standard of care. And of course, we were exposed to some of the early data from these randomized trials at the American Society of Hematology Annual Meeting in December. And overall, there was the suggestion of a possible benefit to CAR T-cell therapy. Could you tell us a little bit about the data that caught your attention and your insights into how to interpret those data? Dr. Syed Abutalib: Yeah, definitely. So as I alluded earlier, right now, the FDA approval is mainly for patients after two lines of therapy in diffuse large B-cell lymphoma. Now what is happening is that this CAR T-cell is trying to move forward into failure after first line of therapy. And in order to do that it is important that they have a comparative arm, which they tried to do in three trials by comparing it with so-called standard of care therapy. However, it must be noted that the standard of care therapy in diffuse large B-cell is not that straightforward for all patients who relapse. So just to give you the background, about 30% to 40% of the patients with diffuse large B-cell lymphoma experience relapse, and 10% are refractory to first line therapy. Now out of these patients, the standard of care therapy applies in real world practice as to the patients who are transplant eligible. For the remaining patients who are transplant ineligible, there is no standard of care therapy. And the list is very long if you look at the NCCN guidelines for those patients. And the patients who are transplant eligible; if 100 patients go to transplant, 50% are cured. And there is a very good track record for this. And the ones who are cured are mainly the ones who are sensitive to chemotherapy, mainly platinum-based chemotherapy. So what these trials that were presented at ASH, one has to understand that what they call standard of care in their comparative arm because what happens is that if you have a comparative arm that is weak, that is not transplant-eligible patients, or the patients don't go to transplant, then your trial would look much better than what it really is. So there were three trials that caught my attention. One is, of course, ZUMA-7, the axi-cel and the second one is the TRANSFORM trial with liso-cel. And the third one is the BELINDA trial, tisa-cel.  ZUMA-7 and BELINDA trial have been published in the New England Journal of Medicine already. So what is important to acknowledge here is that the patients in ZUMA-7 were refractory to frontline therapy. About 74% of those patients were refractory, meaning that they did not respond to [INAUDIBLE]. Now we don't know how bad the refractory disease was, and ideally, these patients, if they are transplant eligible, which most of the patients were, would have gone to auto transplant, and 50% of them historically would be cured and the other patients who are relapsed within 12 months to frontline therapy. Now in ZUMA-7, they assumed that these patients who are early relapse will not respond to standard of care transplant. They divided those patients to CAR-T versus transplant or non-transplant. The reason I say non-transplant, because only 36% of the patients who were on ZUMA-7 received what you call, ‘standard of care therapy,' high dose chemotherapy with transplant. So I don't think it was a fair comparison to standard of care therapy. Now the other thing is the follow up is not too long as it is for the auto transplant. So it remains to be seen how things will evolve. In the TRANSFORM trial, which was with the liso-cel, the large cell lymphoma group were either primary refractory or relapsed within 12 months. Again, they assume that the patients who relapsed early will not respond to platinum-based therapy. Ideally, these patients should go for auto-transplant. In BELINDA trial, what is significant is that only 23% of the patients received auto transplant. And out of the three transplants, BELINDA trial was the only one which did not show improvement in median event-free survival compared to the standard of care. The hazard ratio was 1.01. So it's difficult to say that these trials are truly positive for CAR-T over auto transplant because they did not compare auto transplant in the CAR-T. They compared all patients with relapsed or refractory disease who could have gotten transplant also to CAR-T, favoring the experimental arm. Dr. John Sweetenham: Yeah, thanks Syed. So I think the take-home message that I'm hearing from you is that there are some interesting signals in these randomized studies about the potential efficacy of CAR-T. It's probably a little bit early to claim victory just yet, and we need to let these studies mature out a bit more and I guess ultimately wait for some overall survival endpoints. You're absolutely right that there is still some uncertainty surrounding the interpretation of these results and the long-term effectiveness of CAR T-cell therapy. One thing there's no doubt about is that CAR T-cell therapy is associated with significant toxicities, the most common being Cytokine Release Syndrome and Immune Effector Cell Associated Neurotoxicity Syndrome, or ICANS. But of course, the list of adverse events is much longer. We recognize late toxicities, including prolonged cytopenias. So right now, CAR T-cell therapy is mainly performed at larger tertiary care centers, but obviously, things are changing as regional facilities begin to do CAR T-cell therapies themselves. And even if they don't actually provide CAR T-cell therapy, a lot of physicians are going to be seeing their patients locally after they have developed toxicities from this treatment. How far have we come, do you think, in managing the toxicities of CAR-T, and how can we better manage those adverse events in our patients as we move forward and it becomes a more widespread intervention? Dr. Syed Abutalib: I believe we are getting better in managing these therapies, but of course, the CAR T-cell therapy is at its infancy, and we are learning. In any case, it is important to understand what are the main toxicities-- as you had mentioned, the CRS and the neurotoxicity and the chronic B-cell achalasia or hypogammaglobulinemia, which basically reflects the persistence of CAR T-cell therapy. So, in an effort to improve on recognition and treatment of these side effects, ASTCT, which is the American Society of Transplant and Cellular Therapy, had the workshop in 2018 in Washington DC, and they published a paper subsequently in trying to educate everybody about these toxicities. What is important in CRS is early recognition, and CRS is divided into different grades according to the ASTCT criteria from grade 1 to grade 4. Grade 1 is when you have fever. Many patients that we will admit or who we will treat who are very sick patients will get fever. One should not assume that it is CRS. We should always exclude the infection and start the appropriate antibiotics. And as a transplanter, we are very well-aware of how to tackle this or as treating hematologic malignancies with a lot of neutropenic fevers. So, if you have fever, appropriate workup should be done. Grade 2 ASTCT criteria is fever with hypotension that does not require pressors or hypoxia that requires low-flow nasal-cannula oxygen. Grade 3 is worsening of the hypotension, requiring pressors without vasopressin or hypoxia getting worse. And grade 4 is an extreme with multiple pressures requirement for hypertension and hypoxia requiring CPAP or BiPAP. So all this requires close monitoring and one should also recognize the risk factors prior to the admission of the patient or prior to giving the CAR-T. What are the risk factors for this CRS. The risk factors, which include our high pre-infusion tumor burden, so it is important sometimes to debulk the patient.  Early onset of fever, presence of underlying inflammatory process or presence of infection--these things will help manage the CRS. The other thing is the neurotoxicity. And similarly, there has been criteria developed for that too.  There's an algorithm at our institution, we have developed a card that has this criteria and algorithm imprinted on it. So, there is an ICE criteria which basically checks for patient orientation. And you have certain questions about ability to name three objects, following commands, writing, and attention. You give them certain points. And then you have them go into the neurotoxicity domain and check the level of consciousness and/or their seizures or motor findings or elevated cerebral intracranial pressures. So based on that, you find out what is their neurotoxicity grade. Having said that, it is also important to have toci, which is IL-6 inhibitor, on hand. And according to the regulatory authorities, these drugs are approved under the REMS program. So you have to have at least two doses of tocilizumab in-house before you give any patient these drugs. So, to answer your question in a nutshell now is that close hemodynamic monitoring is very important, and it is important to have trained staff on board who can check on patients at regular, frequent intervals to recognize these toxicities early and intervene early to prevent morbidity and mortality. Dr. John Sweetenham: Yes, thanks. And I think it emphasizes the fact that the initial patient selection for CAR T-cell therapy is extremely important bearing in mind not just the patient's disease state but also age, performance status, co-morbidities, and so on in the same way, really, as with transplant. I want to change gears just for a moment. There is no doubt that cellular immunotherapies like CAR-T remain of limited availability in part because of cost and effectiveness barriers. And without getting into a long discussion about that, I wonder if you could comment a little bit on other emerging therapies that in time could potentially, if it's the right expression, challenge CAR T-cell. I'm thinking in particular about some of the bispecific T-cell engaging antibodies which are now coming online. Dr. Syed Abutalib: Sure. So the bispecific antibodies are basically protein constructs with a specificity to two different antigens. And they commonly bind immune effector cell antigens and tumor-specific antigens, creating what we call an immune synapse, which results in activation of the effector cells, which are T-cells, and cause direct cytotoxic activity. For example, we have an FDA-approved agent in ELL, and it's also listed in NCCN as an-- in transplant-ineligible patients, which is blinatumomab, which is a CD3 and CD19 construct. Now in the clinical trials, there are many bispecific antibodies that are in development. The benefit of this is manifold, in my opinion. They are off-the-shelf immunotherapy. They have strategies to mitigate CRS and neurotoxicities such as that they are given those adjustments with lower rates of doses early on and then the dose is escalated. And we see less CRS and neurotoxicity in patients. The third advantage is they might be preferable, especially in older adults.  I'm not sure if they are going to replace the auto transplant at this time. The other advantage is that there is data emerging that they are effective even after CAR T-cell therapy failures although the data is not mature yet. And still, we need them to be approved and see how they will be in the real world setting. So some of them I will talk about. The one that really caught my attention was mosunetuzumab, which is called mosun. The unique thing about this is that it's IV, and there is a step up dosing to mitigate the CRS and neurotoxicity as I mentioned.  And it is a time limited therapy. It's not that you have to keep going, and that is important because of the cost effectiveness of the therapy. And this is a CD3 and CD20 construct. It is being tested in the third line follicular lymphoma as monotherapy in combination of Revlimid. The important thing is that the CR grade 3 and grade 4, very few patients, 2 patients out of 90 in follicular lymphoma, and no grade 4, grade 5 events occurred whether with monotherapy in follicular lymphoma with a CR rate of about 58%. They are also being combined with polatuzumab, which is an anti-CD79 antibody and also in relapsed/refractory diffuse large B-cell lymphoma as a subcutaneous dose because of, again, further trying to mitigate the CRS with a slow release form. The other important biphasic antibody is glofitamab, which is being tested in relapsed/refractory follicular lymphoma, relapsed/refractory mantle cell lymphoma after BTKI, failures. And also, the data in more than 200 patients was presented in patients with diffuse large B-cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma, Richter syndrome. So these two are very important to watch for. There are others, such as epcoritamab, which is also C3 and CD20 bispecific antibody, which is also in a phase III trial, what is the standard of care in relapsed/refractory diffuse large B-cell lymphoma, and is also being tested upfront with R-CHOP. So I think these three are important to watch out for, and in my opinion, which might be incorrect, these are, as I alluded earlier, are more convenient, less laborious, can be less CRS, and might have about similar-- might have similar activity as CAR-T, might win the game over CAR-T. But it's too early to say. It's just an opinion. Dr. John Sweetenham:  Thanks, Syed. And I think however this plays out, however, ultimately, these bispecific antibodies line up versus CAR T-cell therapy, I think two things are true for sure. The first of those is that patients with aggressive lymphomas and indolent lymphomas now have available to them a number of treatment options they didn't have before, which, of course, is great news. The second thing which is undoubtedly true is at least for a while, CAR-T therapy is with us to stay. Syed, it's been a pleasure having you on the podcast today and hearing your insights into how CAR T-cell therapy is evolving and its potential to improve patient outcomes in the future. Dr. Syed Abutalib: Thank you, John. Dr. John Sweetenham: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness   Dr. Syed Abutalib: None Disclosed   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.  

In this podcast episode,Charise Gleason, MSN, NP-BC, AOCNP, discusses clinical considerations for patients with multiple myeloma after relapse on initial therapy. Topics in this podcast include:Strategies for monitoring for disease progressionDisease, therapy, and patient considerations for treatment selection at first relapseNursing implications and supportive care considerations for patients receiving therapy for relapsed diseasePresenter:Charise Gleason, MSN, NP-BC, AOCNPAdvanced Practice Provider ChiefWinship Cancer InstituteAdjunct FacultyNell Hodgson Woodruff School of NursingEmory UniversityAtlanta, GeorgiaCE/AAPA credit available by visiting the online program: https://bit.ly/3ee9IvsLink to full program, including downloadable slidesets:https://bit.ly/3ee9Ivs

In this podcast episode, Beth Faiman, PhD, MSN, APRN-BC, AOCN, discusses clinical considerations for diagnosis and optimal treatment selection for initial management of patients with multiple myeloma. Topics in this podcast include:IMWG criteria for diagnosing smoldering and active myelomaRisk stratification of smoldering myeloma with 2/20/20 criteria and active myeloma with R-ISS stagingIndividualizing initial treatment for ASCT-ineligible myelomaSelecting optimal initial treatment for ASCT-eligible myelomaPresenter: Beth Faiman, PhD, MSN, APRN-BC, AOCNNurse PractitionerCleveland Clinic Taussig Cancer InstituteCleveland, OhioCE/AAPA credit available by visiting the online program: https://bit.ly/3ee9IvsLink to full program, including downloadable slidesets: https://bit.ly/3ee9Ivs

In this podcast episode, Suzanne Lentzsch, MD, PhD, and  Saad Z. Usmani, MD, MBA, FACP, discuss how they select optimal treatment for relapsed/refractory (R/R) multiple myeloma (MM) and answer audience questions from a live webinar. Topics include:Selecting optimal triplet regimen after first relapseSequencing treatment options after multiple relapsesManaging patient expectations when selecting treatmentsEmerging treatment options for R/R MMPresenters:  Suzanne Lentzsch, MD, PhDDirector, Multiple Myeloma and Amyloidosis ProgramProfessor of MedicineDivision of Hematology/OncologyColumbia University Medical CenterNew York, New YorkSaad Z. Usmani, MD, MBA, FACPClinical Professor of MedicineDepartment of Hematologic Oncology & Blood DisordersDivision ChiefPlasma Cell Disorders DivisionLevine Cancer Institute/Atrium HealthCharlotte, North CarolinaSupported by educational grants from Amgen; Bristol-Myers Squibb; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; and Oncopeptides.Link to full program, including an downloadable slidesets and an on-demand webcast:https://bit.ly/3gjr62p

When should myeloma vaccines be used for patients? Dr. Syed Abbas Ali, MD of Johns Hopkins Medicine joins Myeloma Crowd Radio to share how post-treatments vaccines could be used to extend remissions after stem cell transplant or when patients are on maintenance and their myeloma is under control.  Dr. Ali shares his open GVAX vaccine study for patients who have low risk myeloma or reasonably controlled myeloma. The vaccine is given to patients in combination with lenalidomide (Revlimid). The goal is to prevent myeloma from coming back and to teach the immune system to kill what might be left following traditional therapy. With this vaccine, some patients can experience a deeper remission and have a longer progression free survival.  Learn more about how vaccines can be used to improve immune system surveillance and boost immune cell functions in this important show.   Thanks to our episode sponsor, Bristol Myers Squibb

Dr. Mitul Gandhi, a medical oncologist specializing in hematologic malignancies at Virginia Cancer Specialists, which is part of the US Oncology Network, highlights key abstracts from the #ASCO20 Virtual Scientific Program that aim to improve outcomes for patients with multiple myeloma. Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. I'm delighted to welcome Dr. Mitul Gandhi, a medical oncologist with Virginia Cancer Specialists, which is part of the US Oncology Network. Dr. Gandhi's clinical and research focus is in malignant hematology.   Today he will highlight key abstracts featured at the ASCO20 Virtual Scientific Program and discuss the potential of new agents and treatment approaches to improve outcomes for patients with multiple myeloma. Dr. Gandhi reports no financial conflicts of interest relating to the issues discussed in this podcast. Full disclosure is relating to all daily news podcasts can be found on our episode pages.   Dr. Gandhi, welcome to the ASCO Daily News Podcast.   Dr. Mitul Gandhi: Thank you for having me. I really appreciate the opportunity to review the abstracts from this year's meeting.   ASCO Daily News: Can you tell us about the abstracts that will likely support new standards of care?   Dr. Mitul Gandhi: So within the world of multiple myeloma, there were several exciting studies that were conducted with investigational agents that are new, and then repurposing existing agents in different lines of therapy. When reviewing this, while it may not change how we practice tomorrow, it certainly informs what may be in the very near future.   I think a representative abstract is 8500, presented by Dr. Richardson and his colleagues, and involved a novel compound CC-92480 in relapsed refractory myeloma. And this is an interesting compound, which is a Cereblon ligase modulator and a next iteration of agent based on the Revlimid and, rather, lenalidomide and pomalidomide mechanism acting on Cereblon and degrading Ikaros and Aiolos.   And this was a phase I study with a phase II expansion based on the maximally tolerated dose. And what they found were that this agent studied in heavily pretreated myeloma patients, all refractory lenalidomide, pomalidomide in the majority refractory to anti-CD38 antibodies. This drug was still able to achieve a response across several dosing cohorts.   They had a complex study design involving twice daily along with once daily dosing, and a 1.0 milligram-per-day dose was identified as a MTD. And at that dose, they found 48% of patients achieved a response, with correlative studies demonstrating degradation in Ikaros and Aiolos consistent with the mechanism of action.    And so what it tells us is that this mechanism still remains a potent avenue for exploitation in spite of progression on first- and second-rate generation compounds like lenalidomide and pomalidomide. So this informs possible changes in the future, where we would continue to use a compound like CC-92480 in spite of progression on the existing agents.   And we can see itself working in earlier lines of study and complexing with other compounds to the increased response rate. So this is something that we think will be relevant in the future if not relevant tomorrow in terms of standard of care.   ASCO Daily News: There have been substantial improvements in survival for patients with multiple myeloma in recent years, thanks to the introduction and widespread use of multiple novel agents and regimens. Are there new treatment approaches or agents in development that people should be aware of?   Dr. Mitul Gandhi: Absolutely. I think this can be viewed in a few ways. As all the listeners are well aware of and have experience with, the monoclonal antibodies on top of the existing backbone of treatment that has led to significant improvement and outcomes with relapsed refractory patients, both with daratumumab and elotuzumab.   Daratumumab, of course, being in an anti-CD38 antibody and elotuzumab targeting SLAMF7. There are next-generation antibodies on the anti-CD38 backbone, such as isatuximab. And that was studied in abstract 8508 in high-risk multiple myeloma by Dr. Weisel and colleagues from Germany.   So this particular study kind of captures what the goal is, which are moving these monoclonal antibodies higher up in the lines of therapy. So this particular trial looked at higher risk multiple myeloma, defined by chromosomal aberrations, such as deletion 17p, translocation (4;14) or (14;16), or excess copies of 1q21.   These patients received isatuximab on top of the KRd backbone, with an option for pursuing stem cell transplantation. There were 50 patients in the initially presented data -- 46 in the transplant eligible; 4 in the transplant ineligible. And one of the striking things that was identified was a 46% complete response rate in a otherwise high-risk cohort.   So this is emblematic of what the field is moving towards, which is incorporating these novel antibodies on top of an established backbone and seeing better response rate that were initially met. And as an increasing amount of data identifies achieving lower and lower myeloma burden and hopefully MRD negativity, minimal residual disease negativity, earlier on, pretending long-term, better outcomes, incorporation of these novel antibodies is one - exciting, and two - it will hopefully help inform the next generation of therapy.   Notably, these results are still preliminary phase II studies. And longer term follow up will be needed to identify if they are better than the existing outcome. Another study in that same vein is abstract 8507, presented by Dr. Zafar and his colleagues from SWOG, incorporating elotuzumab with the RVd backbone for, again, newly diagnosed, high-risk multiple myeloma.   They define high risk in a similar vein as a German group with translocation (14;16), (14;20), 17 p or gain of 1q21. And they took 103 patients, randomized them to RVd or RVd plus elotuzumab. They found at 53 months median follow up, a relative similarity in the progression-free survival. 31 months for RVd and 34 months for elo RVd with a P value of 0.449.   And there was no overall survival observed, albeit that truncated follow up. Notably, there were higher rates of response with the incorporation of elotuzumab. And so what this study validated is it's certainly using the proteasome inhibitor backbone. But maybe switching the antibody to increase response rates has, at least at this first analysis, there was no improvement in PFS.   Nonetheless, I think it's an important study, as the goal seems to be incorporating novel compounds on top of an existing backbone to improve depth of response. So these are two representative abstracts, which shows where the field is moving. And the patients that are relapsed and refractory, a slew of other studies targeting anti-BCMA are particularly exciting and relevant.   The DREAMM-6 study, abstract 8502, presented by Dr. Nooka,  used belantamab, which is an antibody drug conjugate targeting the BCMA B-cell maturation antigen conjugated to a cytotoxic payload. And in heavily pre-treated penta-refractory patients, they achieved an impressive response rate, with a clinical benefit rate of almost 80%, which is exciting, as these are patients with limited treatment options.   This is a novel mechanism of action with evidence of excellent responses, many that seem to be durable. It did have a unique toxicity profile, which is increasingly being recognized with cutaneous toxicity. So incorporation of opthalmology and identification of mitigation strategies are going to be important as more familiarity is gained.   But there are a number of further studies that are being pursued with belantamab. In context of this, there were three cellular therapy protocols also presented -- abstract 8503 by Dr. Munshi and colleagues, and abstract 8504 by Dr. Mailankody and colleagues, and abstract 8505 by Dr. Berdeja and colleagues. All three were abstracts around cellular therapy using a CAR T construct targeting BCMA with three different compounds.   And all three looked at similar patient populations with heavily pretreated patients. Abstract 8503 by Dr. Munshi looked at 140 patients penta-refractory and triple-class refractory that were treated with this compound in escalating doses. They found at the highest dose cohort at 450 times 10 to the 6 cells, an overall response rate of almost 82%, many of them durable with durability at median of 11 months.   This was associated with cytokine release storm along with some neurotoxicity, both at night, rather, at 96% and 20%, respectively-- but well managed. Similar findings were found on the other cellular products. Orvacabtagene presented by Dr. Mailankody on abstract 8504 and a Juno product in abstract 8505 by Dr. Berdeja. There was evidence of cytokine release and neurotoxicity in both. But again, with significant response rates in heavily treated patients, many of them durable. So altogether, it shows that an  extension beyond what we discussed initially, where there is next generation of compounds on existing mechanism of actions, these series of abstracts are looking at incorporation of monoclonal antibodies, improving on outcomes in first-line therapy, along with targeting BCMA through either an antibody drug conjugate or through cellular therapy, eliciting responses in very heavily pre-treated patients. Many of them are durable. But with a unique set of toxicities ranging from cutaneous to cytokine release storm.   ASCO Daily News: Dr. Gandhi, are there any other clinical trials that really stood out for you this year?   Dr. Mitul Gandhi: So a few other abstracts I think that are worth noting, with respect to the clinical trials question, I think with the data that's been presented in the abstracts we've talked about, they inform the next generation of studies as we build upon the outcomes that were presented for more mature data, longer term data, and novel combinations.   A few other studies that I think were informative -- abstract 8509, presented by Dr. Kumar and colleagues, involving venetoclax plus bortezomib and dexamethasone in relapsed refractory myeloma. This was interesting because we know that venetoclax seems to have preferential sensitivity and rearranged (11;14) patients for BCL-2 high.   And what the study found in a randomized fashion of 291 patients-- 194 to the venetoclax arm and 97 of the placebo-- in the patients that had a rearranged (11;14) translocation were felt to have BCL-2 high, median duration of PFS was not reached compared to 9.9 months in the placebo arm.   So this is an impressive targeted therapy in a subset of patients. It seems to enjoy very long-term responses in spite of being heavily pretreated with venetoclax, which is a drug that's increasingly gaining experience across a wide swath of hematologic malignancies. And so it speaks to the heterogeneity of this disease and perhaps targeting on a more genomically stratified approach with these targeted compounds.   There are a few other studies I think might be relevant for practical matters on a day-to-day basis in the clinic. One of them was 8518, presented by Dr. Ailawadhi and colleagues, regarding the use of RVd in newly diagnosed myeloma with renal impairment. As we know, many of our patients can present with myeloma-associated kidney dysfunction, whether through light-chain deposition disease or a cast nephropathy with high light-chain levels.   And there sometimes is a bit of a trepidation in administering Revlimid in this setting out of concern for toxicity in the setting of depressed GFR. They performed a retrospective analysis and found that even in patients with baseline depressed GFR ranging from less than 30 or between 30 and 60, the incorporation of lenalidomide helped achieve almost equivalent outcomes in patients compared to patients who had a preserved GFR greater than 60.   So in their transplant-ineligible patients, for example, they found a median PFS of 36 months compared to 30 months in people with and without creatinine clearance less than 60. In their transplant-eligible patients, interestingly, they found a PFS of 48 months versus 43 months in the same cohort. So this speaks to the ability to safely administer this drug in achieving nearly equivalent outcomes compared to the people who have baseline intact kidney function.   So with appropriate monitoring, modification of dosing, and attention to myelosuppression, it seems as though we should be using lenalidomide-based induction therapy, which we would otherwise would if the patient's GFR was preserved and still able to achieve long-term durable responses.   A couple of other smaller studies that I think are worth mentioning include abstract 8515, presented by Dr. Cornell and colleagues, regarding bortezomib induction in light-chain amyloidosis prior to autologous stem cell transplant. There has been some question regarding what the best induction strategy is in patients who presented with light-chain amyloid.   And so this was a retrospective analysis of the CIBMTR database. We're looking at patients who had received a bortezomib-based induction versus no induction prior to proceeding with a stem cell transplant using high-dose melphalan. And it was fairly clear in their followup that a bortezomib-based induction was associated with decreased risk of relapse within two years -- 13% in the bortezomib arm versus 22% in the patients that presented directly to transplant -- and translated into overall longer PFS as well.   So this validates the use of bortezomib in patients prior to stem cell transplantation in a niche population with amyloid. Similarly, abstract 8516, presented by Dr. Zhang and colleagues, questioned whether the incorporation of an alkyqlating agent on top of this proteasome inhibitor backbone would help in these patients with light-chain amyloid.   There has been an increased use of cyclophosphamide, bortezomib, dexamethasone induction based on smaller phase II studies. So this group looked at retrospectively a bortezomib plus an alkylating backbone versus one with bortezomib alone. And found that the overall hematologic response rate was fairly similar -- 73% in the patients that received bortezomib plus an alkylator versus 85% that did not, which was not statistically significant.   So it seems as though while there is a temptation to use the alkylator, it may not be necessary. And bortezomib alone may be sufficient. But of course, it would be on a case-by-case basis. But it adds to the body of literature regarding how to treat these patients with amyloid. So I thought those were helpful analyses in a smaller population but which may be relevant tomorrow in clinic.   ASCO Daily News: Well, thank you, Dr. Gandhi, for sharing your valuable insights on these promising developments in this field.   Dr. Mitul Gandhi: Thank you for the opportunity. I appreciate it.   ASCO Daily News: And thank you to our listeners for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us on Apple 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor Dr. Michael Williams will discuss some of the new research in lymphoma that was presented at the 2018 American Society of Hematology Annual Meeting, held December first through fourth in San Diego, California. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center, and Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. ASCO would like to thank Dr. Williams for discussing this topic. Dr. Williams: Hello. This is Michael Williams. I'm a professor at the University of Virginia Health System in Charlottesville, Virginia, and I'm reporting today on some exciting advances in lymphoma that were presented at the Annual Meeting of the American Society of Hematology, which was held in San Diego, California in early December 2018. Well, there were a number of areas of lymphoma that had important reports, and I'm going to just give you a small sampling of these today. We'll start with a new treatment option for patients with follicular lymphoma. Traditionally, this type of lymphoma, when it's symptomatic and needs therapy, the treatment of choice has been chemotherapy combined with a monoclonal antibody such as rituximab or obinutuzumab. But investigators, in a multicentered trial, decided to test whether you could use a chemotherapy-free treatment approach for patients like this by using rituximab combined with lenalidomide, which is also known as Revlimid, as a substitute for chemotherapy. And this is based on the fact that Revlimid plus rituximab has synergistic activity in patients with relapsed disease, so maybe we could see acceptable, high responses when it would be compared directly with rituximab plus chemotherapy. So the way the trial worked is this. Patients who needed therapy, who had advanced-stage follicular lymphoma—they had never had any therapy before—were randomized to either the rituximab-lenalidomide combination or a rituximab-chemotherapy combination that could include the regimens CVP or cyclophosphamide, vincristine, prednisone, the same combination given with daunorubicin, or the CHOP regimen, or rituximab combined with bendamustine. So over 1,000 patients were treated in this multinational study and the goal of the treatment, of the study was to prove that, actually, the ritux-lenalidomide was superior to the chemotherapy regimens. So the results showed, not superiority, but comparability. The complete remission rate between rituximab-len and ritux-chemotherapy were really identical, 48 and 53 percent, and the 3-year likelihood that the patients were progression-free, so had had no recurrence of their disease, was identical as well: 77 to 78 percent. There was no difference in survival which was 94% at 3 years in both arms. The toxicities differed, however. There was more rash with the lenalidomide combination, whereas low blood counts and the need for growth factor support such as G-CSF was greater with chemotherapy. And it was also interesting that some of the traditional risk factors didn't seem to apply, as much, for lenalidomide. So what would be considered higher risk patients treated with chemotherapy, seemed to do somewhat better with the lenalidomide combination. The importance for a patient with untreated follicular lymphoma who needs therapy is that a chemotherapy-free approach with rituximab plus lenalidomide can be considered equivalent to rituximab-chemotherapy. It’s worth discussing this with your oncologist when you're considering what treatment to use initially. The next subtype of lymphoma that I want to discuss is diffuse large B-cell lymphoma, and there's 2 presentations that I'm going to summarize. One, in patients with advanced stage disease, meaning stage III or IV. This identifies patients who have disease both above and below the diaphragm, to make it stage III, or stage IV means they've got bone marrow or other sites of involvement such as liver or bone. And the question being asked in this trial, which was part of the International GOYA trial, will take just a moment to explain. So the original GOYA trial compared whether a newer form of anti-CD20 monoclonal, namely obinutuzumab, which is also called Gazyva, how that would compare with the standard established monoclonal antibody, rituximab. And the initial findings of this study found that there was no benefit for the newer antibodies. So rituximab and CHOP chemotherapy was equivalent to obinutuzumab and CHOP chemotherapy in overall outcomes. But there was an opportunity with this trial to answer a question that's been out there for many years, and that is how many cycles of treatment does one need? So the investigators took advantage of this large study which included 712 patients who were randomized to rituximab plus CHOP. Just over 500 of them received 6 cycles, and the remaining 186 received 8 cycles. Even the patients who got 6 cycles of CHOP chemotherapy also got an additional 2 doses of rituximab, so the immunotherapy monoclonal antibody was equivalent between the 2 arms. And the results of this showed that there was really no difference at all with a followup of about 3 years. Response rates were equivalent and there was no difference in the patients staying in remission. It didn't matter in terms of survival which was excellent in both arms. There was, however, more toxicity in patients who received 8 cycles, including cardiac problems, infections, etc. These results showed that, I think we can finally put to rest the use of 8 cycles of rituximab-CHOP chemotherapy for advanced-stage large cell lymphoma. It's been an unknown entity because we never had a direct comparison of these. So we can now say that 6 cycles plus the additional 2 doses of rituximab is a standard for advanced-stage diffuse large B-cell lymphoma. Now, what about patients who have limited-stage, so stage I or II diffuse large cell lymphoma? That means just a single lymph node area's involved or 2 adjacent lymph node areas. In the past, these were treated either with 6 cycles of rituximab-CHOP or sometimes cycles of R-CHOP plus local radiation therapy. And in this study, which took a long time to complete; it began in 2005, but it enrolled 592 patients who were then randomized to either 4 cycles or 6 cycles of treatment. Radiation therapy was not planned for any of these patients except for very specific locations of involvement such as testicular DLBCL where radiation therapy is a standard. So the take-home message after over 5 years of follow-up for patients on this study showed that 4 versus 6 were identical. So 89% of patients were still in remission at 3 years after completing treatment, and the overall survival was really impressive, 98 to 99 percent in the 2 arms. So there was no benefit with limited-stage favorable disease. Now, who are these patients? So younger than age 60, stage I or II disease, and normal LDH. They did not have bulky disease, meaning there was no nodal mass more than 7 and a half centimeters. So if you fit those criteria, then you can benefit from a de-escalation of treatment and be spared the additional 2 cycles of R-CHOP. Now, sticking with the topic of diffuse large B-cell lymphoma, a challenging problem in our field is for patients who relapse after their initial therapy, or in some cases, fail to respond to a treatment like rituximab-CHOP or an equivalent immuno-chemotherapy regimen. And a very exciting advance in the field, over the past few years, has been the development of chimeric antigen receptor T cells or CAR Ts. Traditionally, what we've done with patients who relapse or have resistant diffuse large cell lymphoma is to give them a second-line, high-dose chemotherapy regimen, and if they showed a good response to that, they could then go to a dose-intensive treatment with a follow-up consolidation by autologous stem cell transplantation. And with that, you can cure, overall, about 40% or so of patients. The CAR T-cell approach takes a very novel immunotherapy effort, and that is that a patient's own T-cells are removed from the peripheral blood, and then in the laboratory, they're modified and reprogrammed so they can attack the patient’s diffuse large B-cell lymphoma cells that are resistant to chemotherapy. So there were 2 important follow-up studies, each of them involved 1 of the agents, the CAR T-cell products, that are approved by the Food and Drug Administration for patients with relapsed or refractory diffuse large cell lymphoma. The first used the CAR T known as axicabtagene ciloleucel. It's quite a complex name, but it goes by the abbreviation of axi-cel or the trade name is Yescarta. So in this study, the investigators wanted to show that this is a treatment that can be extended to many centers with the product, the CAR T being made in a central facility by the pharmaceutical company. So it was a retrospective study of 295 patients at 17 international centers: a lot of patients across a broad spectrum of sites in North America and Europe. Virtually all the patients were able to develop and obtain a CAR T product. It included patients with some of the higher risk forms of the DLBCL such as double and triple-hit lymphoma. About 3% of patients died during the treatment, although only 1% of these were felt to be related to the treatment itself. The response rates were quite good, with about 80% of people responding. The complete remission rates at 30 days after the CAR T infusion were 47%. So it proved that you can use this centrally manufactured product. So the patients T-cells are collected at the local center, they're shipped to the manufacturing facility, the CAR Ts are generated, sent back to the home institution, and then infused. And I'll say a word in a moment, after I introduce the next paper, to explain some of the side effects of this treatment. So the second study was also presented at the ASH meeting and published simultaneously in the New England Journal of Medicine in early December 2018. So this used the second FDA approved CAR T known as tisagenlecleucel or Kymriah. In this study, there were 93 patients who were able to receive a CAR T-cell infusion, 40% of them achieved a complete remission, and another 12% had a partial response. And that a year after their documented response, two-thirds of these patients were maintaining the response, including 79% of those who achieved a complete remission. So this trial again confirmed across multiple centers that CAR T-cells can be an effective therapy. The side effects of both of these drugs can include something called cytokine release syndrome where the immunologic effects, essentially, release cytokines into the blood that can mediate a capillary leak, respiratory troubles, and low blood pressures, that can, in some cases, require intensive care unit support. This can be managed by other mediators that tamp down the cytokine effect such as an interleukin-6 antagonist. The other toxicity which is less well understood and problematic can be neurologic effects which can include confusion, speech alterations and even coma. But again, approaches and treatments to identify and manage this are being developed. So CAR Ts have become established. They're available at a number of centers, but it's important to consider this as a treatment option in the setting of relapsed or refractory diffuse large cell lymphoma. The long-term curability is still unknown, although it's encouraging that patients with very resistant disease who'd get a good response can maintain that response out to a year and more. So we're going to be very interested to see how the longer-term follow-up comes together. The final topic I wanted to mention today is Waldenstrom macroglobulinemia. So this is a unique form of indolent B-cell lymphoma where the lymphoma cells release a monoclonal immunoglobulin into the blood known as IGM. Now, IGM is a very large antibody, and because of that, when the levels are very high, patients can have problems with high viscosity or thickening of the blood, which can cause confusion, vision changes, sometimes respiratory problems. And these patients also can become anemic or develop enlarged lymph nodes or enlarged spleen. So one of the standard treatments for this disease is, again, the immunotherapy monoclonal antibody rituximab, but the responses are typically incomplete and somewhat short-lived. So it was exciting, a couple of years ago, when the targeted tyrosine kinase inhibitor, ibrutinib, which targets the bruton tyrosine kinase in malignant B-cells. This is an agent that's approved in chronic lymphocytic leukemia, and certain lymphomas such as mantle cell, marginal zone, as well as lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. So here's the study. Investigators had shown that if you combine rituximab with ibrutinib, that the response rates were improved as compared with rituximab by itself. And in a follow-up study that looked at this over a longer period of time, these benefits of the combined therapy were confirmed. These included patients without prior treatment or with prior treatment, with either chemotherapy or rituximab. And there was a confirmed benefit for the ibrutinib-rituximab combination in patients, whether they had had treatment before or not, and regardless of certain genetic markers that we use to assess risk in Waldenstrom. It was also shown that because these treatments continue indefinitely, as long as patients are responding and tolerating therapy, that the response rates improved over time. The side effects of treatment with ibrutinib are well-known, now, after several years of use across a variety of diseases, as mentioned, and include diarrhea, sometimes rash. You can see problems with easy bruising or bleeding, atrial fibrillation, and sometimes skin rash, or muscle and joint aches. But most patients are able to continue therapy and to benefit from it over an extended period of time. So the combination of ibrutinib plus rituximab was shown to add benefit compared with rituximab alone, and again, is a treatment approach and option that you could consider whether you have previously untreated or relapsed Waldenstrom macroglobulinemia. So overall, it was a very exciting meeting. We've had practice-changing data presented, and I've given you just a sampling of those. I think it's important for anyone dealing with lymphoma, or related malignancy, such as CLL or multiple myeloma to be very encouraged by the progress in the field, the opportunity to get much better responses with less toxicity and with minimal or no use of traditional chemotherapy. So we're pleased to be able to offer these treatment approaches for our patients. And I thank you for your taking part in the podcast and hope you found it useful. Thanks again. ASCO: Thank you, Dr. Williams. Learn more about lymphoma at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. Cancer.Net is supported by ASCO’s Conquer Cancer Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

At last year's ASH meeting, there was excitement around a new antibody drug conjugate targeting a protein called BCMA from Glaxo Smith Klein. Results from their Phase I study showed that patients who had relapsed immunomodulators (like Revlimid), proteasome inhibitors (like Velcade) and even monoclonal antibodies (like daratumumab), responded when taking this drug alone (60% response rate). Learn more from Dr. Maria Chaudhry of Ohio State University about current studies using this new drug and when patients could consider it in the course of their treatment.  Thanks to our episode sponsor, Celgene. 

PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Pfizer, Novartis, Roche, Sanofi, Uk Biobank, GSK, Regeneron Genetics, AriSla, Nerviano Medical Sciences, Trovagene, Menarini, Eli Lilly, AIFA, Merk, Aiom, Newron e Zambon.Persone: Amy Brown (EP Vantage), Maurizio de Cicco (Roche), Andrea Agazzi (NMS Group), Romano Marabelli (Ministero della Salute), Dan L. Longo (Università di Harvard), Carmine Pinto (Aiom), Federica Meloni (Università di Pavia).Nuove terapie: Humira, Revlimid, Ocrevus, Dupilumab, PCM-075, imatinib, avelumab, deflazacort, safinamide, evolocumab.Patologie: sclerosi multipla, dermatite atopica, sclerosi laterale amiotrofica, leucemia mieloide cronica, carcinoma a cellule di Merkel, mesotelioma pleurico maligno, distrofia muscolare di Duchenne, malattie cardiovascolari. Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Per approfondire gli argomenti visita il sito web www.PharmaPills.it e clicca mi piace sulla pagina facebook “PharmaPills”.Per segnalazioni sugli argomenti da trattare in questo podcast puoi scriverci su pharmapills [at] carrieranelfarmaceutico.com mentre per ulteriori informazioni e nuovi contenuti in tempo reale ti invitiamo invece a unirti al canale telegram telegram.me/pharmapills. Aiutaci a crescere con una recensione a 5 stelle su iTunes!Gli autori di PharmaPills sono:– Linda Scannavini (voce e regia)– Giorgia Latteri (montaggio e regia)– Stefano Lagravinese (coordinamento e regia)

PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: Pfizer, Novartis, Roche, Sanofi, Uk Biobank, GSK, Regeneron Genetics, AriSla, Nerviano Medical Sciences, Trovagene, Menarini, Eli Lilly, AIFA, Merk, Aiom, Newron e Zambon.Persone: Amy Brown (EP Vantage), Maurizio de Cicco (Roche), Andrea Agazzi (NMS Group), Romano Marabelli (Ministero della Salute), Dan L. Longo (Università di Harvard), Carmine Pinto (Aiom), Federica Meloni (Università di Pavia).Nuove terapie: Humira, Revlimid, Ocrevus, Dupilumab, PCM-075, imatinib, avelumab, deflazacort, safinamide, evolocumab.Patologie: sclerosi multipla, dermatite atopica, sclerosi laterale amiotrofica, leucemia mieloide cronica, carcinoma a cellule di Merkel, mesotelioma pleurico maligno, distrofia muscolare di Duchenne, malattie cardiovascolari. Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Per approfondire gli argomenti visita il sito web www.PharmaPills.it e clicca mi piace sulla pagina facebook “PharmaPills”.Per segnalazioni sugli argomenti da trattare in questo podcast puoi scriverci su pharmapills [at] carrieranelfarmaceutico.com mentre per ulteriori informazioni e nuovi contenuti in tempo reale ti invitiamo invece a unirti al canale telegram telegram.me/pharmapills. Aiutaci a crescere con una recensione a 5 stelle su iTunes!Gli autori di PharmaPills sono:– Linda Scannavini (voce e regia)– Giorgia Latteri (montaggio e regia)– Stefano Lagravinese (coordinamento e regia)

In the news this week, the launch of NeuroCDRD – a new initiative to accelerate development of treatments for neuro diseases; OICR researchers invent a new molecular barcode technology; and Aurinia Phramceuticals prices a US$150.5 million public offering of common shares. We have all this and more coming up on Biotechnology Focus Radio. Story 1 Our first story this week highlights Calgary, AB’s Oncolytics Biotech® Inc. The company has entered into a collaborative research project  with cancer charity Myeloma UK and multi-national biotech firm, Celgene.  In the joint initiative Myeloma UK has launched MUK eleven, a first-of-its-kind immunotherapy trial that aims to modulate the immune system to target myeloma. The Phase 1b trial will study Oncolytics immuno-viral therapy and lead product REOLYSIN®, in combination with Celgene Corporation's immunomodulatory drugs (IMiDs), Imnovid® (pomalidomide) or Revlimid® (lenalidomide), as a rescue treatment in relapsing myeloma patients. MUK eleven’s chief investigator Gordon Cook, Consultant Haematologist at Leeds Teaching Hospitals Trust  says this trial is about taking a new approach of activating a patient's own immune system to target their myeloma (immunotherapy) using a natural virus and lenalidomide or pomalidomide. REOLYSIN will be combined with Celgene's Imnovid® or Revlimid® in patients whose myeloma is progressing while on these IMiD treatments. The dose escalation trial will look at the safety and tolerability of these combinations, and will investigate whether the addition of REOLYSIN extends disease control in this patient group. This clinical study expands on earlier pre-clinical work by Professor Cook that demonstrated that REOLYSIN has dual modes of action against multiple myeloma; being both directly cytotoxic and also activating immune effector cells to target and destroy cancer cells. Further, this immune-mediated activity can be enhanced by immunomodulatory agents to eliminate disease. The trial will aim to recruit 44 patients across up to six Myeloma UK Clinical Trial Network centres in the UK. MUK eleven is part of the Myeloma UK Clinical Trial Network, a portfolio of early stage trials coordinated by the Clinical Trials Research Unit at the University of Leeds, focused on testing and speeding up access to promising new treatments for patients. Story 2 In a unique public-private partnership, Montreal’s Cyclenium Pharma Inc. and Toronto’s Hospital for Sick Children (SickKids) have entered into a research agreement designed to facilitate the discovery of novel modulators for multiple new and existing biological targets of pharmacological interest across a variety of disease areas, including cardiovascular, immunology and oncology.  Cylenium is a company focused on discovery and development of novel drug candidates through the use of its proprietary macrocyclic chemistry. The collaboration will give SickKids researchers immediate access to the company’s QUEST Library™ of next generation macrocyclic molecules and associated chemical hit and lead optimization capabilities. The initial objective of the partnership is to identify compounds capable of interacting with specific therapeutic targets being studied at SickKids, thereby providing tools to improve the understanding of their involvement in the pathophysiology of specific diseases, with the ultimate goal of discovering novel therapeutic or diagnostic agents. Cyclenium president, CSO and CEO Dr. Helmut Thomas.adds that his company’s library will be made available to researchers through the SickKids Proteomics, Analytics, Robotics & Chemical Biology Centre (SPARC BioCentre). The SPARC BioCentre is a high-throughput drug screening facility at SickKids. One of the first studies to be initiated involves targets implicated for the treatment of cancer and immune disorders. For Cyclenium, this is the latest in an extensive series of international discovery collaborations established with prominent companies and research institutions to explore the exciting potential of its unique macrocycle chemistry technology, including Astellas Pharma, Haplogen GmbH, Fundación MEDINA, German Cancer Research Center (DKFZ), McGill University/Goodman Cancer Research Centre, Institute for Research in Immunology and Cancer (IRIC)/Université de Montréal, and Southern Research Institute. Story 3 Clinical-stage drug developer Aurinia Pharmaceuticals last week announced the pricing of secondary public offering for gross proceeds of approximately $150.5 million US. As part of the offereing the company is selling 22.3 million shares at $6.75 per share. Leerink Partners LLC and Cantor Fitzgerald & Co. are acting as joint book-running managers for the Offering, that is expected to close March 20th. The cash will be very beneficial as the Victoria-based company intends to initiate a Phase 3 trial for its lead drug candidate, voclosporin, in treating lupus nephritis. The trial will commence in the second quarter. The drug successfully went through a positive 48-week data phase 2b trial in 2016 and 2017, and seems on track to becoming the first drug to demonstrate a clear benefit for the disease. As an aside, Aurinia’s stock had hit an all-time high of $10.50 per share on March 13, the eve of the public offering announcement. By offering its shares at $6.75 the next day, new investors received a 36 percent discount. Canada’s Motley Fool reported that while it may seem as if investors are getting a raw deal, it should be noted that the stock began 2017 at just $2 per share. Motley Fool further commented that there are only 53.45 million shares outstanding today, and the company ended 2016 with less than $40 million in cash. In other words, while the number of shares will be diluted by 41.7%, the company will more than quadruple its cash. Story 4 In Toronto,  a team of cancer researchers have identified a protein biomarker expressed on the surface of tumour cells in high-grade serous ovarian cancer, the most common and lethal subtype of the disease. The findings, featured on the cover of the March 7 issue of Cell Reports, show that patients with high levels of the biomarker, CD151, have a poor prognosis, says lead author Mauricio Medrano, a molecular biologist and research associate at Princess Margaret Cancer Centre, University Health Network. “Ovarian cancer is many diseases,” says Dr. Medrano. “By identifying CD151 and its underlying role in cancer cell survival, we hope to develop a therapy to target it. As a marker for poor prognosis, with further research, there is the potential to develop a clinical screening tool to help personalize cancer treatment for patients.” The research was led by principal investigator Dr. Robert Rottapel, senior scientist and Professor, Departments of Medical Biophysics and Immunology, University of Toronto. In lab experiments, the research team used cell lines derived from 40 patient tumour samples to identify that CD151 contributes to the survival of cells of high-grade serous ovarian cancer origin. The team further analysed tissue samples from a cohort of approximately 1,000 patients to establish the correlation of high levels of CD151 to poor prognosis. Dr. Medrano says the study provides a lot of new information about other possible targets, not only CD151, that could be important and can provide new ideas for how to target ovarian cancer.” The research was supported by the Ontario Institute for Cancer Research, Ovarian Cancer Canada, the Canadian Ovarian Cancer Research Consortium’s biobank funded by the Terry Fox Research Institute, and The Princess Margaret Cancer Foundation. Story 5 Also In Toronto, Researchers at the Ontario Institute for Cancer Research (OICR), together with international collaborators, have invented a technique to avoid a major problem with common laboratory techniques and improve the sensitivity of important cancer tests. The findings, recently published in the journal Nature Protocols, describe a process by which the sensitivity of DNA sequencing can be improved. The technology, called SiMSen-Seq, could aid in detecting the recurrence of cancers, catching possible disease relapses faster than current methods and improving patient outcomes. Essentially the scientists have created a DNA barcode with a hairpin structure that as Dr. Paul Krzyzanowski, Program Manager of OICR’s Genome Technologies Program explains opens up to be read when heated and contracts when cooled. This allows researchers to ‘hide’ the barcode and analyze more patient DNA fragments in a single reaction he says. Cirrently, for DNA sequencing, scientists often use a technique called polymerase chain reaction (PCR) to increase the amount of DNA available from a sample. However, PCR can introduce mistakes that can limit researchers’ ability to detect real mutations in the original DNA molecules. To track the original molecules in a sample, molecular tags called DNA barcodes are added. This technique is essential for sensitive detection of mutations but can lead to other errors, as components of the tags can interfere with each other and affect the final results. Dr. Krzyzanowski led the development of analysis pipeline software used in SiMSen-Seq which flags errors in sequencing results and corrects them computationally. Current genome sequencing technologies return results with error rates of about one per cent, meaning that for researchers to be certain that a mutation exists it has to be detected in a sample at a rate of greater than one per cent. Dr. Krzyanowski says that the SimSen-Seq technology has lowered this error rate 100-fold, meaning that the recurrence of cancers could be detected at lower levels and earlier than before, allowing patients to receive additional treatment sooner. His team has already patented the technique, and while it can conceivably be performed in any molecular biology lab, the group also hopes to make their expertise in using the method available to the research community. Those interested in accessing this service can do so through OICR’s Collaborative Research Resources directory. Story 6 In our final story, three leading players in Canada’s health sciences sector are joining forces to create a novel drug development platform that will help advance new therapeutics for some of the most debilitating conditions such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, and Parkinson’s disease. The initiative, under the banner of ‘NeuroCDRD’, is jointly led by The Centre for Drug Research and Development (CDRD), the Montreal Neurological Institute and Hospital at McGill University (MNI), and Merck. Its initial focus is the creation of a high-content hiPSC (human-induced pluripotent stem cell) screening platform that will help researchers better model neurological disease. Development of new drugs for neurological diseases has long been hampered by the lack of predictive humanized models, and many treatments that have looked promising in animal studies have in turn failed in subsequent human clinical trials. To mitigate this challenge, this new collaboration will use the MNI’s renowned hiPSC platform and bring together experts from MNI’s neurological and CDRD’s drug screening and assay development teams to develop a new generation of disease-specific research models using patient-derived hiPSCs. The idea is to significantly reduce research timelines and costs, making it possible to develop future hiPSC models for neurological diseases with smaller patient populations. As Gordon McCauley, President and CEO of CDRD explains this collaborative initiative not only combines the cutting-edge science of academia, that it will also benefit from CDRD’s translational abilities, and the commercial resources of a top industry partner like Merck. “By working together, we are a catalyst for Canadian life sciences leading the world,” he said. And that wraps up another weekly episode of the Biotechnology Focus RADIO. A special shout out to Laskey Hart who works tirelessly to produce each weeks show, and to the Biotechnology Focus research team for tracking this weeks stories.  As we’re always on the lookout for your story ideas and podcast suggestions we’d love to hear from you our listeners, to let us know what’s hot on the Canadian biotech scene.  Be sure reach out to us via twitter @biotechfocus, or by email at  press@promotivemedia.ca with your suggestions. And of course, you can also catch up on past episodes online via our podcast portal at www.biotechnologyfocus.ca .

Det kommer allt fler nya mediciner för patienter med sällsynta och allvarliga sjukdomar. Kaliber granskar särläkemedlen som hjälper svårt sjuka men kostar så mycket att det går ut över annan vård. - Jag har då inga njurar som fungerar, så jag ligger i dialys fem dagar i veckan a fyra timmar. För att rena det dina njurar gör i vanliga fall, gör den här maskinen åt mig.Hur mår du när du ligger här?- Det är väl okej, det blir ju väldigt mycket tid av ens liv att ligga i maskin. Du har ganska ont när man sticker med metallnålar som är ganska grova för att kunna få den här dialysmaskinen att fungera och få ett bra flöde. Blodet går grunt hela tiden, ju fortare blodet går runt desto bättre dialys får jag.Hanna ligger under en gul filt i en sjukhussäng i Halmstad. Persiennerna är neddragna och blodet pumpas runt genom plastslangar och en maskin som renar det, en behandling som heter dialys.Hanna har den ovanliga och livshotande sjukdomen aHUS, atypiskt hemolytiskt uremiskt syndrom. Den leder till blodbrist och till slut slås njurarna ut.- AHUS för mig är ett liv i maskin, som det ser ut nu. Och det finns då ett läkemedel som gör det möjligt för mig att få en njure och blir transplanterad och slippa maskinen 20 timmar i veckan, och tillbringa den tiden med min familj och mina barn.Soliris är det första läkemedlet för patienter med aHUS.Det kan göra Hanna frisk.Och är, per patient och år, bland de dyraste läkemedlen i världen.Cirkapriser: Soliris 4,5 miljoner kronor per patient och år, Vimizim 3,8 miljoner, Kyprolis 2,5 miljoner.Kaliber idag handlar om priset för särläkemedel, det vill säga nya läkemedel för patienter med ovanliga och allvarliga sjukdomar.För att få fram nya och bättre särläkemedel har EU infört regler som gynnar läkemedelsbolagen. Och nu ser vi resultatet fler nya läkemedel och högre kostnader i sjukvården.I Sverige hamnar kostnaden på landstingen och staten.Samtidigt som de nya läkemedlen kan hjälpa svårt sjuka med sällsynta sjukdomar så trängs annan vård undan. En svår ekvation.Kaliber har tittat närmare på två av de dyraste särläkemedlen, Soliris och Translarna.- Vi står i vårt kök och det är ganska stort för att killarna ska kunna köra med sina rullstolar här inne.I det här röda huset med vita knutar bor Carin. Hon är mamma till två pojkar med den ovanliga och allvarliga muskelsjukdomen Duchennes muskeldystrofi. Huset är ombyggt för att pojkarna ska kunna växa här med sjukdomen. Det saknas trösklar och i hallen finns en stor vit hiss. För sjukdomen förvärras med tiden.- Och sen toaletten är lite större, med höj- och sänkbara handfat. Sen är det stort utrymme för att kunna använda just en stol inne i duschen eller senare kanske en brits för att kunna duscha. Så man har ju sett lite framåt.Tänker du framåt? - Jag vågar nästan inte det. Det är ju lite läskigt. Det är lite skrämmande. Man vet ju lite grann om det man har läst om sjukdomen. Men man försöker att inte tänka på det hela tiden. För att orka med att leva så måste man glömma bort det ett tag.Men du vet att det kommer att hamna en brits här?- Ja, så kommer det ju att bli. Förhoppningsvis så sent som möjligt.Duchennes muskeldystrofi drabbar ungefär tio personer i Sverige varje år, oftast pojkar. Muskelfibrerna bryts succesivt ned, den motoriska utvecklingen stannar av. Det är vanligt att drabbade inte längre kan gå vid tio års ålder.Det nya läkemedlet Translarna kan bromsa sjukdomsförloppet. Det kan hjälpa ungefär var tionde patient, och det är bara de som kan få läkemedlet.I Sverige är det Carins söner och ett tiotal till som får Translarna. I dagsläget får Carins yngsta son det av läkemedelsbolaget. De flesta andra har fått det för att de varit med i en studie.- Det här är ju vårt hopp som vi lever på. Vårt hopp för framtiden. Det känns som att den gör väldigt bra för Rasmus.Cirkapriser: Translarna drygt 3 miljoner kronor per patient och år. Procysbi 1,6 miljoner, Revestive 2,2 miljoner, Vyndaqel 1,2 miljoner. - Hej, tjena välkommen!En som jobbar med att göra bedömningar om nya särläkemedel är värda sitt pris, om de är kostnadseffektiva, är Lars Sandman. Han är professor i hälso- och sjukvårdsetik vid Linköpings universitet och också etisk rådgivare till NT-rådet, landstingens gemensamma organ som tar fram rekommendationer om nya läkemedel ska användas i landstingen.- Det som blir problematiskt är naturligtvis att vi skulle kunna säga att ett liv är oändligt mycket värt, vi borde kunna lägga hur mycket som helst, då riskerar vi ju liv i en annan ände av systemet. Lägger vi otroligt mycket på en patient eller en liten patientgrupp så kommer andra patienter att bli utan, vi förlorar liv i den andra änden i stället. Så i någon bemärkelse kommer vi alltid att ställas inför problemet att vi faktiskt måste sätta ett pris på ett liv, hur obehagligt det än kan kännas.Nya dyra läkemedel för sällsynta sjukdomar väcker alltså frågan vad ett läkemedel för en patient får kosta. Och de ställer landstingen inför ett dilemma - vård ställs mot annan vård.Att det har kommit fler särläkemedel är ett resultat av att USA, Japan och EU har infört regler som gynnar läkemedelsföretagen. Systemet i EU gör att bolagen bland annat får ensamrätt för ett särläkemedel i tio år och därmed ingen konkurrens om priset.I EU är det europeiska läkemedelsmyndigheten, EMA, som godkänner särläkemedel. För att klassas som ett särläkemedel ska det rikta sig mot ovanliga sjukdomar som är livshotande eller innebär mycket allvarliga tillstånd och så ska läkemedlet vara mycket bättre än de som redan finns eller innebära en helt ny behandling för sjukdomar där det tidigare saknats behandling.Samtidigt som fler allvarligt sjuka kan få ett bättre liv så varnar den internationella organisation OECD för de ökande globala kostnaderna.Läkemedelsbolagen ökar försäljningen och marknaden går starkt framåt.EvaluatePharma jobbar med statistik och rapporter kring läkemedel.- Hello. Oh my name is Lisa Urquhart. I am editor of EP Vantage, which is a part of EvaluatePharmaEvaluatePharma ser en enorm utveckling.2010 såldes särläkemedel för 70 miljarder dollar globalt.Förra året var siffran 102 miljarder dollar.Och 2020 förväntas försäljningen vara uppe i 178 miljarder dollar.- Its growing quite strongly, actually. Its growing at 11 percent annually.Marknaden för särläkemedel växer med runt 11 procent per år och det är dubbelt så mycket som den totala läkemedelsmarknaden växer.Det är en attraktiv marknad, bland annat för att läkemedelsbolagen kan ta ett högt pris och för de regler som ger bolagen ekonomiska fördelar, säger Lisa Urquhart.- I think its a very attractive market as well, particularly for drug developers. Because, mainly, the prices that developers can take and the fact that there is limited competition.Det finns ingen statistik över hur mycket särläkemedel säljs för i Sverige.Kaliber har därför tagit fram nya, unika siffror i samarbete med SKL, Sveriges kommuner och landsting.Vi har kollat vad de läkemedel som idag klassas som särläkemedel av EU kostade i Sverige 2015.Och summan blev närmare 1,2 miljarder kronor. Det är ungefär fyra procent av landstingens kostnader för läkemedel.Årsnota: Revlimid 239 miljoner, Soliris 130 miljoner, Vidaza 52 miljoner, Elaprase 49 miljoner, Vyndaqel 34 miljoner. Kostnaderna för särläkemedel hamnar till större del på landstingen än vad övriga receptbelagda läkemedel gör.Det beror på att särläkemedlen i större utsträckning är utanför högkostnadsskyddet och subventioneras då inte av staten.De flesta landsting och regioner, 19 av 21, svarar i en enkät som Kaliber har gjort att kostnaderna för särläkemedel ökar.Flera landsting uppger också att de ökande kostnaderna för särläkemedel går ut över annan vård. - Hej, Anders Carlqvist söker jag.Anders Carlqvist är läkemedelschef i Västra Götalandsregionen: - Det finns ju alltid en alternativ användning av alla pengar. Om du lägger pengar på något så kunde du ha lagt de på någonting annat, och alla vet ju att det finns behov inom vården, så att någon viss undanträngningseffekt är det alltid.De ökande kostnaderna gör att sjukvården hamnar inför svåra avvägningar om de resurser som finns, säger han.- Alltså man skulle önska att man kunde ge all behandling till alla patienter som behöver det. Men nu är det så att gapet mellan vad som är möjligt att göra medicinskt och med läkemedel och de resurser som finns ökar.Kaliber kan konstatera att nästan alla landsting lägger mer och mer pengar på särläkemedel.Behandlingarna tränger undan annan vård samtidigt som de kan vara livsavgörande för svårt sjuka patienter.Hur mår du? Hur känner du dig?- Huvudvärk, yr, lite skakig är man ju absolut efter varje behandling.Vi återvänder till Hanna, som precis har avslutat fyra timmar i dialys.Hon kom hit från jobbet som sjuksköterska och ska hem till barnen.- Livet fortsätter ju även om jag ligger fastlås i en maskin.Hanna är en av omkring 45 personer i Sverige som lider av sjukdomen aHUS.För henne är det självklart att landstingen ska bekosta medicinen.Hur tänker du kring prissättningen? Det är ju läkemedelsbolaget som sätter priserna. Har du tänkt något kring det? - Det krävs ju oerhörda forskningsresultat och forskning bakom till att få fram ett sånt här läkemedel och jag tänker att det någon gång måste betalas tillbaka.Trots att läkemedlet Soliris och njurtransplantation skulle göra att Hanna slipper den här dialysmaskinen och att Translarna skulle bromsa den allvarliga muskelsjukdomen hos Carins barn, så är det inte självklart att de får behandlingarna.Det beror på att läkemedel, trots att de är godkända som särläkemedel i EU, kan bedömas vara för dyra eller ha för dålig effekt i förhållande till priset i Sverige.Det är NT-rådet som ger rekommendationer till landstingen om ett läkemedel bör användas eller inte.Rådet är landstingens gemensamma organ där NT står för nya terapier.I dagsläget avråds landstingen från att använda ett tiotal särläkemedel.Det kan bero på att läkemedlen bedöms vara för dyra i förhållande till vilken effekt de har, eller att det ännu inte har utretts hur kostnadseffektiva de är.Stefan Back är ordförande i NT-rådet:-Vid extrema kostnader så är det ju så att det blir ju undanträngningseffekter också. Det ska ju också vara en jämlikhet och solidaritet mot andra sjukdomstillstånd och andra behandlingar inom landet, så att man inte får undanträngningseffekter. Vi är ju satta just för att göra de här kostnadseffektivitetsbedömningarna och övervägandena.Varför är det då viktigt att komma med sådana här rekommendationer?- Ja, vi vill ju ha tillgång till läkemedel på samma sätt i hela Sverige. En jämlik läkemedelstillgång och läkemedelsanvändning.Meningen med att avråda från ett läkemedel som anses för dyrt eller där effekten är otydlig är alltså att vården ska vara rättvis och jämlik i hela landet oavsett vilken sjukdom man har.Men NT-rådets rekommendationer ifrågasätts. När NT-rådet i juni 2015 rekommenderade landstingen att inte ge behandling med Soliris för sjukdomen aHUS väckte det debatt. En som var kritisk till NT-rådets beslut var Diana Karpman, överläkare i Region Skåne och professor i pediatrik vid Lunds universitet.- Det går helt emot läkarkoden att avstå en behandling som finns och som dessutom är extremt effektiv. Så om du frågar mig som läkare så är det förstås oacceptabelt. Däremot kan jag förstå resonemanget att det är för dyrt. Resonemanget är att, om man tar samtliga särläkemedel, så är det en enorm kostnad om man tar allihop. Men varje särläkemedel för sig, för den patientgruppen den ska bota är inte så dyr. Det är bara ett fåtal patienter, så det är liksom ingenting.Hanna, som har haft sjukdomen aHUS i 14 år, är också kritisk till NT-rådets beslut.- Det handlar om en så stor livskvalitetändring för den som får Soliris, så man kan inte prata kostnad. Dels kan personen få gå tillbaka till jobb och samhället slipper betala massa sjukpengar till personen i fråga.Soliris är dokumenterat väldigt effektivt, till skillnad från vissa andra särläkemedel. Så i det här fallet handlar NT-rådets beslut enbart om priset, som ju läkemedelsbolaget sätter.NT-rådets ordförande Stefan Back:- Hade det varit ett dåligt läkemedel och lika dyrt, då hade det varit ett väldigt enkelt beslut. Likadant om man har sjukdomar som inte påverkar möjligheten för fortsatt liv. Är behandlingen extremt dyr, så är det inte alltid man får ett ok från oss.Så vad är grundproblemet?- Grundproblemet är prissättningen.Hur ser ni på den?- Det är företagets roll. Det är de som sätter priset, vi sätter inte det.NT-rådet har kommit med två olika rekommendationer för Soliris för två olika sjukdomar, aHUS och PNH. PNH är också en ovanlig sjukdom, som runt 60 personer i Sverige har. Här är NT-rådets rekommendation lite öppnare, de som bedöms verkligen behöva läkemedlet bör få behandlingen.När det gäller läkemedlet Translarna så är NT-rådets rekommendation att de pojkar som varit med i studier får fortsatt behandling om läkemedlet har en effekt man kan se. Men NT-rådet avråder från att nya patienter behandlas med Translarna eftersom man vet för lite om hur effektivt det är i förhållande till kostnaden, säger ordföranden Stefan Back. Vi vet ju inte vilken prisnivå det hamnar på och vilka effekter som finns på läkemedlet, om det är försvarbart eller inte.Även det beslutet har lett till kritik, bland annat från Mar Tulinius, professor vid Göteborgs universitet och överläkare på Drottning Silvias barnsjukhus. Han har lett en av studierna av Translarna och har ägnat många år åt att diagnosticera och behandla barn med muskelsjukdomar.- Jag är övertygad om att desto tidigare man kan börja med läkemedlet desto bättre effekt når man på lång sikt. Och allt som kan hjälpa dem att förlora funktioner lika fort är bra.Så kostnaden spelar mindre roll egentligen?- Jag tycker att det är försvarbart att ha den kostnaden med tanke på att allt som bromsar upp den här sjukdomen ökar livskvalitén så pass mycket och gör att pojkarna behåller funktion längre. Så på det sättet tycker jag att det är samhällsekonomiskt försvarbart.- Rasmus börjar du bli redo? Är du redo? Då får du ställa dig i startposition Spring så fort du kan Heja dig hejaheja heja.Rasmus, som har Duchennes muskeldystrofi och får Translarna, är mitt uppe i tester här på Drottning Silvias Barnsjukhus i Göteborg. Var tredje månad går han i trappa, testar hur långt han kan gå på sex minuter, lyfter vikter, springer på tid och blåser i maskin.Mamma Carin väntar utanför.- Jag tycker inte att man kan sätta nåt pris på ett barns liv. De är värda hur mycket som helst. Ovärderliga. Mina barn är ju min dröm som gick i uppfyllelse. Så det känns jättekonstigt att det ska behöva kosta så mycket.Vad tycker du om ett läkemedel som kostar tre och halv miljon kronor per år och patient? Är det rimligt?- Jag tycker att det är helt vansinnigt. Det är svårt att förstå det som vanlig förälder liksom.Var ska vi kapa kostnaden? - Det är väl läkemedelsbolagen i första hand som kan kapa dem, tror jag. För det finns ju ett behov av det, så det borde kunna gå att sänka kostnaden för det och få in pengar ändå.På andra våningen i ett kontorshotell i Göteborg sitter Roger Johansson som är vd för den nordiska delen av PTC Therapeutics, vars viktigaste produkt är Translarna. Vi vill veta varför bolaget har satt priset som de har gjort.- Här sitter vi. Välkommen! Vi har två små rum härTranslarna kostar drygt 3 miljoner kronor per patient och år och tillhör därmed de dyrare läkemedlen.Även om försäljningen beräknas öka med 150 procent i år, så har bolaget ännu inte gått med vinst och enligt PTC har det har tagit 18 år och kostat 4,5 miljarder kronor att utveckla läkemedlet.- Lång utvecklingskostnad, stora investeringar och få patienter. Då får man den här typen av kostnadsläge på ett läkemedel.Vad säger du om priset? - I ett företag så måste det finnas nåt slags incitament för att starta detta. Det är också därför man har ett regelverk som hanterar särläkemedel. Man stimulerar företag att forska och utveckla den här typen av läkemedel och då måste det finnas en möjlighet att också tjäna pengar och få tillbaka det man investerar. För oss kommer det att dröja många, många år ens om vi någonsin kommer break even, trots att vi har det prisläget som vi har. Det är det svaret jag har.Soliris är alltså ett av de dyraste läkemedlen i världen. Det kostar uppemot 4,5 miljoner kronor per patient och år. Även överläkaren Diana Karpman, som arbetar med svårt njursjuka barn som blir hjälpta av Soliris tycker att läkemedelsbolaget Alexion har satt ett orimligt pris. - Jag tycker det är enormt. Alltså priset är ofattbart enormt. Vinsten är enorm. Den diskussionen måste man ta för att de har vissa lättnader och incitament för att utveckla läkemedel. Det tar flera, flera år att utveckla. De har monopol i ett antal år. Så då får man ha en diskussion med läkemedelsindustrin om prissättningen.Alexion har sålt Soliris för över 10 miljarder dollar sen 2008, enligt årsredovisningarna. Succén har lett till att bolaget under samma period gjort en vinst efter skatt på 2 miljarder dollar.- Det är klart att det är exceptionellt stora siffror, när det är en produkt som riktar sig till en mindre patientgrupp. Sätter man det i sitt sammanhang, så ser vi då att i läkemedelsindustrin så är det en tydlig trend mot mera specialist- och nischläkemedel. Och den här prisfrågan blir också aktuell förstås, säger Johan Unnerus, analytiker på Swedbank.Kaliber har försökt att få en intervju med Alexion. Vi vill veta varför priset är satt som de är, hur Alexion ser på kritiken om att Soliris är orimligt dyrt och om bolaget har planer på att sänka priset. Enligt kommunikationsavdelningen i Schweiz har Alexion inte möjlighet att ge en intervju, men kan svara på våra frågor via mejl.Bolaget svarar i ett uttalande att det är ungefär 100 personer i Sverige som har de två sjukdomarna PNH och aHUS, att Soliris har ett stort värde för vården och att det lilla antalet patienter innebär en begränsad kostnad för landstingen.Men Alexion svarar inte på frågorna om varför bolaget har satt priset som man har gjort. Det finns olika uppfattningar om priset ska kunna sätta stopp för ett läkemedel.Det är ett komplext problem där många gånger höga kostnader för läkemedel till enskilda patienter med svåra sällsynta sjukdomar ställs mot annan vård.Vi har därför tittat närmare på om landstingen ändå gett de särläkemedel som NT-rådet avråder ifrån. Och vad det får för konsekvenser. Kalibers granskning visar att landsting har gett särläkemedel som till exempel Soliris trots att NT-rådet avrått att ge behandling. I Västra Götalandsregionen säger de att man följer NT-rådets rekommendationer och att de är viktiga, men i vissa fall måste beslut om enskilda patienter ändå fattas.Regionen har till exempel gett en patient behandling med Soliris och en patient Translarna efter NT-rådets avrådan. För i slutändan är det den behandlande läkaren eller kliniken som får besluta att ge läkemedlen ändå.Vi frågar Anders Carlqvist, som är läkemedels- och hjälpmedelschef där, vad en rekommendation då spelar för roll?- I vissa fall, som de du nämner nu, så spelar dem ju inte så stor roll.Vad blir konsekvensen på det stora hela?- Alla pengar har ju som jag sa en alternativ användning. Och nåt annat blir inte gjort eller nån kö blir längre, eller någonting.I Region Skåne får alla aHUS-patienter som drar nytta av Soliris läkemedlet, enligt överläkare Diana Karpman. Hon är med i den expertgrupp i regionen som beslutar om en patient ska få Soliris eller inte.Hon anser att NT-rådets rekommendation öppnar upp för orättvisor eftersom det i slutändan är läkare eller kliniker som fattar besluten.- Ja, det gör det eftersom de har fattat beslut på gruppnivå, vilket innebär att man kan på en individuell nivå fatta andra beslut. Där kanske inte finns expertis i just den här sjukdomen, för de är sällsynta sjukdomar. Och då kan skillnaden vara mellan liv och död beroende på var du bor i landet. Vilket egentligen inte är acceptabelt, tycker jag.Vi återvänder till NT-rådets etiska rådgivare Lars Sandman, professor i hälso- och sjukvårdsetik. Han tycker att det är viktigt att landstingen följer rekommendationerna för att vården ska vara jämlik._ Det finns ju också en risk om vissa landsting är duktiga på att vara följsamma medan andra inte är det så finns det en risk att de landstingen spelas ut mot varandra, både i relation till patienter, till professionen, men också i relation till läkemedelsföretag, eller de som producerar de här läkemedlen.Vad blir konsekvensen då? Jag tror att den stora konsekvensen är dels att det upplevs som orättvist att vissa patienter får de här läkemedlen som vi har sagt nej till och andra inte.Behandlande läkare har stor makt över om patienter ska få ett särläkemedel eller inte. Och de behöver alltså inte följa NT-rådets avrådan.Kalibers granskning visar också att läkare som är med och fattar såna beslut kan ha kopplingar till läkemedelsföretaget som säljer läkemedlet de beslutar om.Till exempel när det gäller Translarna.Studien, som nyligen avslutades, bekostades av läkemedelsföretaget PTC och leddes av överläkare Mar Tulinius. Samtidigt som han i sin roll som överläkare inom Västra Götalandsregionen är med och beslutar om patienter ska få Translarna så är han också rådgivare åt PTC och har fått ersättningar från bolaget.- Jag har fått konsultarvode för att delta i vissa möten och någon enstaka gång även för att hålla föredrag för kollegor.Hur ser du på din delaktighet i att få ut läkemedlet och samtidigt ha lyft ersättning från läkemedelsbolaget? - Jag ser det som två helt olika saker. Det som har jag fått arvode för har handlat om en specifik uppgift där jag har deltagit med min erfarenhet av läkemedlet. Och jag kan inte se hur man skulle kunna undvika att ha den typen av möten. Man måste ändå få samla den kunskap som finns hos dem som har den kunskapen. Jag har inte fått betalt för att göra studierna, det tror jag är väldigt viktigt.Det har inte påverkat dig på något sätt. Att du har lyft en ersättning?- Nej det tycker jag inte. Jag kan inte se att det har påverkat mig på något sätt. Det har inte varit den typ av arvoden.När det gäller Soliris har läkemedelsbolaget Alexion bekostat en internationell studie som överläkare. Diana Karpman var samordnare för i Sverige. För det fick hon betalt av Alexion.Karpman har också hållit föreläsningar på Alexions utbildningar. Men hon har då inte tagit betalt, säger hon.- För studien fick vi ersättning för att det var genom landstinget, så det är reglerat. Men man kan tacka nej till arvode för föreläsningar och det gör jag. För min del är det så att jag bedriver forskning inom detta område och vill vara oberoende av läkemedelsföretaget för att min forskning ska vara oberoende.Efter att systemet i EU med att få fram fler nya särläkemedel infördes, så har det har det också blivit fler särläkemedel på marknaden. Men det har också lett till svåra ekonomiska avvägningar i sjukvården. Det finns också kritik mot att läkemedelsbolagen sätter orimliga priser.Vad det gäller framtiden så är ett hundratal nya särläkemedel på väg. Och kostnaderna förväntas öka ännu mer.Det är ett komplext problem utan enkla lösningar.Flera vi har pratat med tycker att systemet behöver förändras för att få ned priserna.En av dem är professor Lars Sandman.- Jag tror att det krävs någon form av förhandling eller kanske någon form reglering på en mer central nivå. Dels kanske vi måste förhandla på en högre nivå, inte bara i Sverige och framförallt inte bara de enskilda landstingen, men lyfta det till en nordisk nivå eller kanske till och med europeisk nivå. Kanske behövs någon form av reglering kring vad som är en rimlig kostnad.För personer med ovanliga sjukdomar kan läkemedlen förändra livet.Numera har Hanna alltid telefonen på och bredvid sig. För hon har blivit lovad läkemedlet Soliris så fort det dyker upp en ny njure så att hon kan göra en njurtransplantation.- Jag har haft tur. Jag har haft ett fantastiskt landsting som har hjälpt mig.Vad kommer att hända när du får Soliris tänker du?- Jag tänker att jag kan träna ännu mer än jag gör idag. Jag kan återgå till mitt jobb som narkossköterska vilket jag älskar och framförallt att jag får en frihet. Och tiden jag tillbringar i den här maskinen slipper jag. Så tiden och livskvaliteten kommer att bli enorm för mig.Reportrar: Daniel Värjö och Samira OthmanProducent: Andreas LindahlKontakt: kaliber@sverigesradio.se

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