Podcasts about Ibrutinib

Play Episode Listen Later Sep 30, 2024 32:48

In this episode, listen to Matthew S. Davids, MD, MMSc, and Lindsey Roeker, MD, discuss BTK inhibitor resistance and how it shapes treatment choices for patients with CLL, including:Contemporary treatment paradigms for patients with CLLSafety and efficacy of current regimensMolecular testing, including when and how to test for BTK inhibitor resistanceConsidering BTK inhibitor resistance when sequencing therapy Program faculty:Matthew S. Davids, MD, MMScAssociate Professor of MedicineHarvard Medical SchoolLeader, Lymphoma ProgramDana-Farber/Harvard Cancer CenterDirector of Clinical ResearchDivision of LymphomaDana-Farber Cancer InstituteBoston, MassachusettsLindsey Roeker, MDAssistant AttendingCLL Program DirectorDepartment of MedicineMemorial Sloan Kettering Cancer CenterNew York, New YorkResources:To review a CME-certified text activity and download slides associated with this podcast discussion, please visit the program page.

conversations care cancer patients md resistance optimizing contemporary cme btk deeper understanding inhibitor cll chronic lymphocytic leukemia sll ibrutinib btki small lymphocytic lymphoma clinical research division matthew s davids

Protective role of neonatal CMV infection in B-ALL; GVHD targets organoid-forming bile duct stem cells; seven-year outcomes for venetoclax-ibrutinib therapy in MCL

therapy medical targets infection conversely stem cells oncology protective medical research bile mrd neonatal hematology duct organoids gvhd tgf ibrutinib year outcomes

Play Episode Listen Later Aug 22, 2024 16:56

In this week's episode we'll learn how cytomegalovirus infection early in life depletes preleukemic cells in a mouse model of B-cell acute lymphoblastic leukemia. After that we'll discuss new research, where GVHD targets organoid-forming bile duct stem cells in a TGF-beta-dependent manner. Conversely, a TGF-beta inhibitor protects these stem cells against GVHD and mitigates biliary dysfunction. Finally, we'll hear about the seven-year outcomes for venetoclax-ibrutinib in relapsed or refractory mantle cell lymphoma. In addition to long-term survival benefits, researchers report durable treatment-free remissions and effective retreatment in patients with MRD-negative complete responses. Featured Articles: Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblasticleukemiaGVHD targets organoid-forming bile duct stem cells in a TGF-β–dependent mannerSeven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses andtreatment-free remissions

Current Clinical Practice and NCCN Guidelines for CLL/SLL

safety profile alpine efficacy sequoia fda approval cll ibrutinib shadman

Play Episode Listen Later Jul 18, 2024 31:33

In this podcast episode, Farrukh Awan, MD, Jeremy S. Abramson, MD, MMSc, and Shuo Ma, MD, PhD, discuss real-world patient cases and how to align current clinical practice with the NCCN guidelines for CLL/SLL, including:Prognostic variables when deciding between regimensRole of MRD in CLLResults from the phase II CAPTIVATE trialChoosing among the available covalent BTK inhibitorsPreferred partner anti-CD20 antibody in CLL/SLLRole of the noncovalent BTK inhibitor, pirtobrutinib, in CLL/SLLUse of CAR T-cell therapy in CLL/SLLPresenters:Farrukh Awan, MDProfessor of Internal MedicineDirector of Lymphoid Malignancies ProgramHarold C. Simmons Comprehensive Cancer CenterUniversity of Texas Southwestern Medical CenterDallas, TexasJeremy S. Abramson, MD, MMScDirector, Center for LymphomaMassachusetts General HospitalAssociate Professor of MedicineHarvard Medical SchoolBoston, MassachusettsShuo Ma, MD, PhDProfessor of MedicineDivision of Hematology-OncologyDepartment of MedicineRobert H. Lurie Comprehensive Cancer CenterNorthwestern University Feinberg School of MedicineChicago, IllinoisContent based on an online CME program supported by educational grants from BeiGene; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; and Lilly, and an independent medical education grant from AbbVie.Link to full program:https://bit.ly/3LzA2As

phd current md llc cart cme captivate clinical practice btk mrd abbvie prognostic rituximab nccn cd20 tp53 ibrutinib janssen scientific affairs nccn guidelines chemoimmunotherapy mdprofessor phdprofessor ighv

Enhancing Treatment Efficacy in Multiple Myeloma at ASCO24

ASCO Daily News

Play Episode Listen Later Jun 24, 2024 22:10

Drs. John Sweetenham and Marc Braunstein discuss practice-changing studies in hematologic malignancies that were featured at the 2024 ASCO Annual Meeting, including the ASC4FIRST trial in chronic myeloid leukemia and IMROZ and CARTITUDE-4 in multiple myeloma. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast. On today's episode, we'll be discussing practice-changing abstracts and other key advances in hematological malignancies that were featured at the 2024 ASCO Annual Meeting. Joining me for this discussion is an old friend, Dr. Marc Braunstein, a hematologist and oncologist from the NYU Langone Perlmutter Cancer Center. Our full disclosures are available in the transcript of this episode. Marc, it's great to have you back on the podcast again. There were some important studies in the heme space at the Annual Meeting this year, and we're very pleased that you're able to share your takeaways. Dr. Marc Braunstein: Thank you, John. It's great to be back again. Dr. John Sweetenham: Let's start out, Marc, with LBA6500. This abstract reports the primary results of the ASC4FIRST trial, and this was a trial comparing asciminib with investigator selected tyrosine kinase inhibitors in newly diagnosed patients with chronic myeloid leukemia. Could you tell us a little about the trial and how you think it's going to impact clinical practice? Dr. Marc Braunstein: Absolutely. So, asciminib is an oral tyrosine kinase of the ABL kinase domain. As we know in CML, the BCR-ABL translocation is characteristic of the disease, and asciminib is approved for chronic phase CML with a T315I resistance mutation or for patients who have received 2 or more prior lines of therapy. So the ASC4FIRST trial was a randomized trial of 405 patients with newly diagnosed chronic phase CML who are randomized one to one to receive either asciminib at 80 milligrams once daily, or investigator's choice of a first generation TKI imatinib or one of three second generation TKIs nilotinib, dasatinib, or bosutinib. The primary endpoint of the study was the major molecular response, or MMR, at 48 weeks. Pretty much, the study met its primary endpoint with a 67% rate of MMR at 48 weeks, with asciminib versus 49% in patients treated with the investigator's choice of TKI. And in addition, the major molecular remission or MMR of 4.5, which is a deep remission, those rates were higher as well, with asciminib versus investigator's choice at a rate of 39% versus 21% when comparing the groups. Furthermore, when we looked at toxicity, there were fewer grade 3 or higher adverse events, with the asciminib at 38% versus either 44% with the first generation, or 55% with the second generation TKI, and fewer discontinuations as well with asciminib. So I think this abstract is practice-changing. I think it offers compelling data to use asciminib upfront for chronic phase CML. Those who don't agree with that sentiment might argue that we want to see longer term follow up. There's a planned follow-up at 96 weeks. We would want to see the rate of progression to acute myeloid leukemia and of course overall survival as well. But I think the abstract certainly shows an improvement in outcomes with asciminib versus our current array of TKIs. Dr. John Sweetenham: Yeah, I think it certainly is, at least at minimum, potentially practice changing. I agree with you. Just one question, and this may be a little bit speculative, but do you have any thoughts about treatment free survival with asciminib and how that might line up against some of the other TKIs? Dr. Marc Braunstein: Yeah, that's a great question. The abstract did not necessarily address that, patients were treated until progression, but we know that with the current landscape of TKIs, that in patients who have achieved a deep MR of 4 or 4.5 for at least 2 years who discontinue their TKI, the rate of relapse is about 50%. The current study, the ASC4FIRST, doesn't address that, but I think it's a really good question about whether, for those patients who have achieved a deep remission, whether they can eventually stop asciminib down the line. Dr. John Sweetenham: Yeah, I guess it's one of those ‘watch this space' things. So we'll see how the data mature out. And let's move on to what I think is another potentially practice-changing study, at least in certain parts of the world. And that's [the] LBA7000 study in classical Hodgkin lymphoma. As you remember, this was a German Hodgkin lymphoma study group trial which looked at the tolerability and efficacy of a novel regimen, BrECADD versus eBEACOPP for patients with advanced stage classical Hodgkin lymphoma in their study, which is known as GHSG HD21. Can you give us your thoughts and take home messages from this trial? Dr. Marc Braunstein: Yeah, John, absolutely. So the German HD21 study is a phase 3 study of 1,500 patients with classical Hodgkin lymphoma. The majority were stage 3 or 4, 84%, that compared two regimens BEACOPP to BrECADD. The major difference between these 2 groups being that the newer BrECADD regimen swaps out bleomycin for brentuximab vedotin, which is an anti-CD30 antibody drug conjugate. Also, in the BrECADD regimen they eliminate vincristine that's incorporated into BEACOPP. Those are kind of the global differences between these 2 regimens. And when comparing these, they looked at the primary endpoint of progression-free survival. Of note, in this study there was a PET adjusted approach where if patients achieved interim PET negativity after 2 cycles, that was followed by an additional 2 cycles of their treatment as opposed to 4 cycles if they were PET positive after the initial 2 cycles of their respective treatment. And of note, there were similar rates of PET2 negativity between both arms, about 58% in both arms. So at a median follow-up of 48 months, the 4-year progression-free survival was significantly better with the brentuximab containing BrECADD regimen at 94% versus 91% with a hazard ratio of 0.66. And the overall survival of the BrECADD arm was 98.6%, which is very high and impressive. The 4-year overall survival was similar between the arms at around 98%, but of note, there were fewer severe adverse events with BrECADD, the brentuximab containing arm versus BEACOPP at about 42% versus 59% and interestingly less peripheral neuropathy with the brentuximab containing BrECADD. So we're doing extremely well in treating advanced stage classical Hodgkin lymphoma. So the bar is set very high. But in this study, the rates of progression-free survival and overall survival are very impressive. While these intensive regimens tend to be used outside of the U.S., there are several notable benefits of the study, including greater than 50% PET2 negativity and high rates of progression-free survival at 4 years. In discussing this abstract, it's worth noting that there are other competing regimens, if you want to call it that, that are more commonly used in the U.S. So the ECHELON-1 study looked at brentuximab AVD compared with ABVD with bleomycin and it was a 94% versus 89% 6-year overall survival rate favoring the brentuximab containing A+AVD regimen. And lastly, more recently, the SWOG S1826 study that hasn't been published but was presented in abstract form looked at nivolumab AVD versus brentuximab AVD at a median follow up of 12 months showed a progression-free survival of 94% versus 86%. And that study still has yet to be published and needs to mature. But both of those regimens are in the NCCN guidelines. So, we're definitely pushing the bar higher in terms of improving responses in treating advanced classical Hodgkin lymphoma. Dr. John Sweetenham: I think that there's no question that these results from BrECADD are very impressive. But I'm taken back to what I think has been a kind of philosophic discussion in Hodgkin lymphoma now for a number of years about balancing disease control and efficacy against the potential short-term and long-term toxicity of the regimens, particularly when you have very effective salvage therapies for those patients who may suffer a relapse. So I think that this is a discussion over whether you take a very intensive, upfront approach to Hodgkin lymphoma versus something that may be less and slightly less intensive. I suspect that's a discussion that's going to continue for a long time. I don't know what you feel, but my own feeling about this is that this study will likely have a major influence over treatment of Hodgkin lymphoma, particularly in western Europe. Less likely in the US.., I would think. I don't know what your thoughts about that are. Dr. Marc Braunstein: Well, it's a great question. In SWOG S1826, that study did include pediatric patients. In HD21, the median age was 31 and did not include pediatric patients. So I think we have to be selective in terms of fitness and which patients may be better suited for different regimens. But I think what all these studies show is certainly when we incorporate novel immunotherapies, whether it's brentuximab vedotin, nivolumab, we improve progression-free survival and even overall survival. Dr. John Sweetenham: Absolutely. So let's shift gears now and take a look at Abstract 7500, the IMROZ study. This was the study of isatuximab, bortezomib, lenalidomide and dexamethasone versus VRD alone for transplant ineligible patients with newly diagnosed multiple myeloma. I know we discussed this in our preview podcast a few weeks back, Marc, but I just wonder now, having seen the data in more detail, what do you think of the important takeaways? And again, are we looking at a new standard of care? Dr. Marc Braunstein: You know, there are many standards of care in multiple myeloma, but we're always looking to make improvements on the regimens we have at our disposal. So, just to recap, IMROZ is a phase 3 randomized study of the anti-CD38 monoclonal antibody isatuximab with the backbone of bortezomib, lenalidomide, dexamethasone or VRD versus VRD alone, specifically, in transplant ineligible newly diagnosed multiple myeloma patients age less than 80. They studied 446 patients in this study, randomized 3 to 2 to Isa-VRD versus VRD alone, with the primary endpoint of progression free survival. Now, similar to other studies where they included a monoclonal antibody up front, the study met its primary endpoint of improving progression-free survival with the quad regimen containing the monoclonal antibody isatuximab versus VRD alone. So what was interesting about the study, it's really the first of its kind to be presented that specifically looked at transplant ineligible patients, which is presumably a less fit or perhaps more frail population that wouldn't go on to consolidation with stem cell transplant. And in this study, the progression-free survival at 5 years was 63% versus 45%, clearly superior when you included isatuximab. And the rates of complete remission and MRD negativity were all significantly improved, too. However, that was also met with slightly more grade 3 or higher treatment emergent adverse events, 92% versus 84% in the control arm. There are also 11% grade 5 treatment emergent adverse events with the isatuximab group versus 5.5% with VRD alone. Although there was no major difference in treatment discontinuation. One small caveat worth noting, too, is that high-risk patients in this study, when presented at ASCO, did not necessarily show a difference in benefit, although there wasn't necessarily a detriment either. So, John, I think that clearly quadruplet regimens are superior in outcomes of efficacy to triplets, even in transplant-ineligible patients. But I think we have to tailor these treatments to individual patients because I think when it comes to transplant-ineligible patients, it's a spectrum of patients who may be more or less fit for quad regimens versus triplet regimens. It's also worth noting, though, that in this study, the patients are really only getting a quad regimen for 4 cycles. They get their Isa-VRD, and then you drop the bortezomib. So when we think about quads, it's not that they're getting the quad regimen indefinitely, it's really for the induction cycles. But still, I think we have to be aware of potential safety issues. Dr. John Sweetenham: Okay, great. And let's stay on the theme of multiple myeloma, Marc, and talk a little bit about Abstract 7504, which was a subgroup analysis of the CARTITUDE-4 study. This is a report on the use of ciltacabtagene autoleucel versus standard of care in patients with functional high risk multiple myeloma. Can you give us your thoughts on this and maybe put it into a bit of context for us? Dr. Marc Braunstein: Absolutely, John. It's really a great time to be in the field of multiple myeloma. We're making tremendous progress, but when we think about one of the unmet needs, it's just consistently the high-risk patients who have shorter responses and are at higher risk for poorer outcomes. Just to review, cilta-cel is one of the 2 available anti-BCMA CAR T-cell products available for the treatment of relapsed or refractory multiple myeloma. Very recently, the FDA approved cilta-cel for lenalidomide refractory patients after 2 or more prior lines of therapy based on the CARTITUDE-4 study, which was published by San-Miguel and colleagues in New England Journal of Medicine in July 2023. And that study randomized 419 patients with multiple myeloma with 1 to 3 prior lines of therapy to receive either cilta-cel or physician's choice of standard of care, which was either 1 of 2 triplet regimens, a pomalidomide, bortezomib, dexamethasone or daratumumab, pomalidomide and dexamethasone. It's worth noting that about 25% of the patients in the CARTITUDE-4 study had prior anti-CD38 antibody treatment previously and the carfilzomib was not included in one of the standard-of-care arms, and we know that those regimens containing carfilzomib do increase survival in relapsed myeloma. Nevertheless, the primary outcome of progression-free survival was not reached in the CAR T-cell arm versus 11.8 months in the standard-of-care arm, with a significant reduction in progression of 74%. So clearly a positive study and CAR T-cell therapy is included in the NCCN guidelines for patients who have an early relapse from their myeloma. The current abstract by Costa et al focused specifically on a subgroup of 79 patients from CARTITUDE-4 in second line of treatment and looked at what they called functional high-risk myeloma, defined as progression of disease within 18 months of initial treatment or after stem cell transplant. Again, the study showed a retained benefit of cilta-cel with significant improvement in progression-free survival either not reached or 12 months with the control standard of care arm, as well as complete remission rate and rates of MRD negativity of 65% versus 10% in the control. The overall survival outcome was still immature and not presented. Nevertheless, cilta-cel is clearly superior to standard-of-care triplet regimens. I think that for patients with high risk, they clearly derive a benefit from CAR T-cell therapy if they have short progression-free survival after initial therapy. Dr. John Sweetenham: Thanks, Marc. So let's round this out by talking about another area of unmet need, I guess in a way in a difficult to treat patient group. And that's Abstract 7007, the SYMPATICO study. This is a study which looks at the efficacy and safety of ibrutinib and venetoclax in patients with mantle cell lymphoma who had a mutated TP53. Can you just briefly review this for us and tell us what you think we should be taking away from this studys? Dr. Marc Braunstein: So, mantle cell lymphoma typically has an aggressive behavior, but the subgroup of patients with a P53 mutation tend to have the poorest outcomes and do represent an area of unmet need. Although BTK inhibitors are making important improvements in mantle cell lymphoma, they have yet to be approved in newly diagnosed mantle cell lymphoma. Acalibutinib and zanubrutinib are FDA-approved BTK inhibitors for previously treated mantle cell lymphoma. Ibrutinib was withdrawn from the market in the U.S. for mantle cell lymphoma. Dr. Michael Wang's group presented late-breaking data from the phase 3 SYMPATICO trial at ASH 2023, in which 267 patients with relapsed refractory mantle cell lymphoma were randomized to receive either ibrutinib plus the BCL2 inhibitor venetoclax or ibrutinib plus placebo after 1 to 5 prior lines of therapy. And that study showed a 32 versus 22 months progression-free survival at a median follow up of 51 months. The current abstract, also by Dr. Wang and colleagues, looked at the subgroup of patients who had a P53 mutation and included an open label cohort of 44 patients in the first line of treatment and a relapse refractory cohort of 75 patients, and compared this subgroup of patients with P53 mutation to those without. When we look at the outcomes, the patients who did not have a P53 mutation clearly did better in terms of progression-free survival being not reached in first-line treatment compared to 22 months progression-free survival in those patients with first-line [treatment] with a P53 mutation. As well as in the relapsed refractory setting, the PFS without the P53 mutation was 47 months versus 21 months with the mutation. However, when you look at these patients treated with ibrutinib and venetoclax comparing whether they got treated in first line or the relapse refractory setting, the overall response rates are very similar at about 80% to 90% and the CR rates were very similar at about 55% to 58%, which to me suggests that although patients with P53 mutation do worse than those without it, whether they're treated in the first-line or the relapse setting with this combination of venetoclax, they tend to do somewhat similar, suggesting that you can overcome resistance to prior therapy in the relapse setting. So I think further data are certainly warranted to explore the role of combination therapies that include novel agents such as BTK inhibitors in the first line setting. It's worth noting that the TRIANGLE study was recently published, and this study looked at including ibrutinib at various phases, including at induction in combination with intensive chemotherapy and during the maintenance phase. And that study showed encouraging outcomes in patients who received ibrutinib even without stem cell transplant compared to those who received stem cell transplant. So the role of BTKIs in mantle cell lymphoma is certainly evolving, and I think it offers a very effective intervention without the same kind of toxicities we see with cytotoxic chemotherapy that's traditionally used in mantle cell lymphoma. But I think the subgroup of patients with P53 mutation in this disease still represent an area of unmet need that unfortunately have worse outcomes. But novel agents may be able to overcome some of those adverse outcomes. Dr. John Sweetenham: Yeah, I agree. I think these are intriguing data, and obviously it needs more follow-up and probably more prospective studies. But nevertheless, I think there are some signals there for sure that need to be followed up on. Marc, as always, it's great to have your insights on key advances in the heme space from ASCO. An important year this year, and we really appreciate your time and effort in sharing with us your thoughts on what we've learned this year. So thank you as always. Dr. Marc Braunstein: My pleasure. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstract discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's guest: Dr. Marc Braunstein @docbraunstein Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Marc Braunstein: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp Speakers' Bureau: Janssen Oncology Research Funding (Institution): Janssen, Celgene/BMS

europe medicine treatments fda ash costa triangle enhancing drs wang cart abstract efficacy abl annual meetings new england journal san miguel hodgkin sanofi immunotherapy btk asco mmr glaxosmithkline mrd abbvie echelon multiple myeloma pfs cml ut southwestern tki asco annual meeting avd nccn tkis tp53 cd38 p53 michael wang ibrutinib adaptive biotechnologies bcl2 vrd sympatico bcr abl transcript dr janssen oncology

BTK Inhibitor-related Cardiotoxicity: Quest for Predictive Biomarkers, Improved Risk Stratification

Oncotarget

Play Episode Listen Later Jun 4, 2024 2:29

BUFFALO, NY- June 4, 2024 – A new research perspective was published in Oncotarget's Volume 15 on June 3, 2024, entitled, “Bruton's tyrosine kinase inhibitor-related cardiotoxicity: The quest for predictive biomarkers and improved risk stratification.” In this new perspective, researchers Jai N. Patel, Jai Singh, and Nilanjan Ghosh from Atrium Health discuss Ibrutinib — the first Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment of patients with chronic lymphocytic leukemia (CLL). “While producing durable responses and prolonging survival, roughly 20–25% of patients experience dose limiting side effects, mostly consisting of cardiovascular toxicities like severe hypertension and atrial fibrillation.” While clinical predictors of BTK inhibitor-related cardiotoxicity have been proposed and may aid in risk stratification, there is no routine risk model used in clinical practice today to identify patients at highest risk. A recent study investigating genetic predictors of ibrutinib-related cardiotoxicity found that single nucleotide polymorphisms in KCNQ1 and GATA4 were significantly associated with cardiotoxic events. If replicated in larger studies, these biomarkers may improve risk stratification in combination with clinical factors. “A clinicogenomic risk model may aid in identifying patients at highest risk of developing BTK inhibitor-related cardiotoxicity in which further risk mitigation strategies may be explored.” DOI - https://doi.org/10.18632/oncotarget.28589 Correspondence to - Nilanjan Ghosh - nilanjan.ghosh@atriumhealth.org Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28589 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, BTK inhibitor, cardiotoxicity, biomarkers, risk, genetics About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

risk quest buffalo reddit improved predictive doi biomarkers btk bruton inhibitor atrium health cll stratification scopus ibrutinib altmetric embase oncotarget jai singh kcnq1

Novel Approaches in Hematologic Malignancies at ASCO24

ASCO Daily News

Play Episode Listen Later May 24, 2024 22:33

Dr. John Sweetenham and Dr. Marc Braunstein look ahead at key abstracts across the spectrum of hematologic malignancies that will be presented at the 2024 ASCO Annual Meeting, including the OPTIC trial in chronic myeloid leukemia, treatment options for transplant-ineligible patients with multiple myeloma, and the 7-year analysis of the ECHELON-1 trial in classical Hodgkin lymphoma. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and the host of the ASCO Daily News Podcast. I'm delighted to be joined again this year by Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center in New York. We're going to be discussing some of the key abstracts in hematologic malignancies that will be featured at the 2024 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode, and disclosures of all guests on the podcast are available at asco.org/DNpod. Marc, it's great to have you back on the podcast. Dr. Marc Braunstein: It's a pleasure to be back, John. Dr. John Sweetenham: There are some exciting abstracts to be presented at this year's meeting, and I would like to begin, if we can, with Abstract 6501. As you know, this reports the four-year results from the OPTIC trial of ponatinib in patients with chronic-phase CML and the T315I mutation. Can you tell us about the trial and about these latest follow-up results? Dr. Marc Braunstein: Sure. Well, we've made tremendous progress in managing patients with CML in the past two decades using these oral tyrosine kinase inhibitors such as ponatinib. Ponatinib is a third-generation TKI that has activity in both Philadelphia-positive ALL as well as CML, and can overcome the resistance mutation you mentioned, called the T315I mutation, which is sometimes found following prior TKI therapy. The OPTIC study is a multicenter phase 2 randomized study of various doses of ponatinib in 283 chronic phase CML patients who had received 2 or more prior lines of therapy or those who had the presence of a T315I mutation, with the current analysis examining the major remission at 48 months, PFS, as well as OS. Of note, in this study, after patients have achieved a major remission with a transcript level of 1% or less, the study allowed for dose reduction of ponatinib from the original dose of either 45 milligrams or 30 milligrams to a reduced dose of 15 milligrams. So, when we look at the results, we find that the patients who had the highest overall response rates and higher rates of molecular remission were those who received the 45-milligram dose. And remember, these patients were allowed to be dose-reduced to the 15-milligram dose once they achieved a molecular remission of 1% or less. In addition, the rates of overall survival were highest in the 45-milligram dose as well. When looking at the T315I subgroup, the rates of molecular remission, the depth of remission, and the rates of progression-free survival, in general, were lower in that subgroup, but still higher in the 45-milligram dose than the 35- milligram dose. Furthermore, when looking at the rates of treatment-emergent adverse events leading to discontinuation, they were 8% in the 45-milligram dose compared to 14% in the 30-milligram dose and 5% in the patients who only received the 15-milligram dose. The authors have concluded that the 45-milligram dose, with the potential to be reduced to 15 milligrams after achieving 1% or less of the BCR-ABL transcript level, seems to be the right balance between efficacy and safety. Dr. John Sweetenham: Thanks, Marc. In the longer term, do you think that this study will, in any way, affect the position of ponatinib in the treatment algorithm for CML? Is it going to remain as a second or third-line option, or do you think there's any chance it will be moved up? Dr. Marc Braunstein: Well, that's a great question. There are other TKIs, such as asciminib, that also target the T315I mutation, and that mutation tends to develop after prior first-line or second-line TKI therapy. But given its activity in both ALL and CML, I think it's certainly reasonable to expect that ponatinib will be used in earlier lines of therapy given its efficacy in later lines. Dr. John Sweetenham: Let's change gears and move the focus to acute myeloid leukemia. There has been a lot of discussion around frailty in many different malignancies, but the impact of frailty on outcomes in AML is maybe something that hasn't been quite so well studied. In Abstract 6506, investigators did a population-based study in Ontario, Canada, that assessed the patient's frailty risk and the impact that might have on outcomes. What are your takeaways from this study, and how do you think these data will help optimize treatment decisions? Dr. Marc Braunstein: Yeah, I'm glad we're talking about this abstract John, because frailty scores are increasingly being used in hematologic malignancies to help guide goals and intensity of care. And as opposed to using age or performance status alone, these composite frailty assessment tools, such as the MFI tool that they used in this particular study, take into account multiple variables that are both physiologic, such as the patient's comorbidities, as well as social, and what kind of support system do they have, and things of that nature. And that accounts for their overall fitness. So, in this retrospective cohort study that was a population-based study in Ontario between 2006 and 2021, they looked at 5,450 patients retrospectively with acute leukemia and grouped those patients into 3 categories based on this frailty index. Patients who are either fit, somewhere in the middle between fit or frail, which they call pre-frail, or frail. And they looked at outcomes such as overall survival, comparing patients who got intensive chemotherapy regimens for induction or those who got non-intensive therapy for induction. Patients in either group could have been assigned to either fit, pre-frail, or frail although there are much more fit patients than those who got intensive induction. And so, looking at their findings, it was noted that patients who were in the frail category, not entirely unexpectedly, had lower overall survival when compared to those who were fit or pre-frail. I think the value of a study like this is not just to highlight the benefit of frailty scores to help predict which patients may ultimately have a shorter survival, but also to help potentially guide which patients may be more suitable for intensive versus less intensive induction. I will note that this study was conducted in an era where we didn't have the same sorts of less intensive induction that are very effective in less fit patients, such as the combination of azacytidine and venetoclax, which is commonly used in less fit patients nowadays. So, the study may encompass patients who didn't have access to that therapy because it wasn't available during that time. But I think it still, overall, does highlight the fact that assessing fitness or frailty in acute myeloid leukemia is important for predictive value. Dr. John Sweetenham: I agree. Marc, I don't know what your thoughts are on this, but it goes either way. I mean, I think that, if I remember the numbers correctly, 25% of fit patients received non-intensive therapy. So, is there a missed opportunity there for that group of patients who actually may have tolerated the intensive therapy but it was never offered? Dr. Marc Braunstein: That's an excellent point, John, and I think that highlights the importance of frailty indices because they take into account much more than one particular factor, or even just a subjective assessment of the patient in real time when they're first presenting. And they may have disease-specific features that are decreasing, say one element of their assessment such as their performance status. So, really taking these composite fitness scores into account may actually allow you to escalate therapy in a patient who may actually be fit but maybe perceived as less fit when they present. Dr. John Sweetenham: Yeah. So, I think, as you mentioned, there are better treatment options out there now maybe than there were at the time this study was conducted. Nevertheless, there may still be that opportunity for more intensive therapy for some of these patients when they are more holistically assessed. Let's move on and switch gears once again and talk about a study in multiple myeloma, the so-called IMROZ study, which is Abstract 7500. So, this is a study looking at treatment options for transplant-ineligible patients with newly diagnosed multiple myeloma. Some of these patients may not have a chance for subsequent therapy if they are not eligible for transplant. What are your thoughts on this study? Do you think we're closer to a new standard of care for patients who are not going to proceed to an autologous stem cell transplant? Dr. Marc Braunstein: It seems like every year there's a new standard of care for newly diagnosed multiple myeloma because there's so much data emerging, which is just wonderful. So, I think as background, at the 2023 ASH meeting, the IsKia study was presented, which is a randomized phase 3 study in newly diagnosed transplant-eligible patients. And that was using isatuximab with carfilzomib, lenalidomide, and dexamethasone upfront and that study did show a benefit in terms of reducing minimal residual disease compared to carfilzomib, lenalidomide, and dexamethasone alone. But that study was looking at fit newly diagnosed patients who were going on to stem cell transplant. Right now, the standard of care for patients who are not eligible for transplant is generally to use a 2 or 3-drug regimen, such as daratumumab, lenalidomide, and dexamethasone, based on the phase 3 MAYA study. But this study is really unique in that it looks at using a quadruplet regimen in patients who are transplant ineligible or not intended to go for transplant. So, the phase 3 IMROZ study was a randomized study of 446 patients that compared isatuximab, bortezomib, lenalidomide, and dexamethasone to bortezomib, lenalidomide, and dexamethasone alone. So, a quad versus a triplet regimen. The primary endpoint in this study was progression-free survival, but they also looked at secondary endpoints, such as complete response rate and minimal residual disease negativity. Just to quickly highlight the results and then discuss the standard of care, the median duration of treatment in this study was 53 months in the quad regimen and 31 months in the control arm. At a median follow-up of about 60 months, the progression-free survival was not reached with the quad regimen versus 54 months in the triplet, and that was a significant difference. In addition, the safety profile was pretty much consistent with the class, there were a bit more grade three or higher treatment-emergent adverse events with the ESA-containing regimen, 92% versus 84%, but no difference in adverse events leading to discontinuation in either arm. So, this study is certainly compelling in terms of using quadruplet-based regimens that contain an anti-CD38 monoclonal antibody for newly diagnosed patients who are not intended to undergo transplant. I think at the meeting, I will be interested to see the patient population that was included. Patients who are over the age of 80, for example, are excluded. So, I would like to know more about their fitness level and performance status. But I think it's clear, John, that using quad regimens over triplet regimens is just consistently superior in terms of efficacy outcomes. Dr. John Sweetenham: Right. I guess that, even though maybe we can't focus on the specific agents right now, it looks as if quad regimens are going to be the standard of care regimens for the future in this group. Do you think that is fair? Dr. Marc Braunstein: Very likely. Dr. John Sweetenham: Absolutely. Well, that's a pretty challenging group of patients. And so to move on again, let's talk about another, perhaps equally challenging group - patients with mantle cell lymphoma, particularly those who carry certain mutations. The so-called SYMPATICO study, which is reported in Abstract 7007, presents data on the efficacy and safety of ibrutinib and venetoclax in patients with mantle cell lymphoma who carry a TP53 mutation. We know that this mutation confers a high risk of early progressive disease and poorer outcomes when these patients are treated with standard chemoimmunotherapy for mantle cell. Trials to date have been limited to small single-arm studies. Can you tell us a little bit about this study and the outcomes and what you think it means for the future? Dr. Marc Braunstein: As a background, although BTK inhibitors such as ibrutinib have yet to be approved for newly diagnosed mantle cell lymphoma, acalabrutinib and zanubrutinib, which are second-generation BTK inhibitors, are FDA-approved for previously treated mantle cell lymphoma. Ibrutinib was withdrawn from the market. The lead author of this abstract, Dr. Michael Wang, had presented a late-breaking data from the phase 3 SYMPATICO trial at ASH last year, in which 267 patients with relapsed or refractory mantle cell lymphoma after one to five prior lines of therapy were randomized to receive the combination of ibrutinib plus the BCL-2 inhibitor venetoclax or ibrutinib plus placebo. That study showed there was a 32 versus 22-month progression-free survival with a hazard ratio of 0.65 at a median follow-up of 51 months, indicating the PFS benefit of the combination of ibrutinib and venetoclax compared to ibrutinib with placebo. So that leads us to this subgroup analysis in the current study being presented at ASCO, in which they looked at a subgroup of patients with mantle cell lymphoma who are at very high risk for treatment failure and early relapse - those are patients who have a mutation in TP53, which again is high risk for treatment failure. This abstract examined an open-label cohort of 44 first-line patients, as well as 75 patients who were in the relapse/refractory cohort, and compared to patients who either did or did not have the P53 mutation. When we look at the progression-free survival outcomes, the median progression-free survival in the first-line cohort of patients who did not have a P53 mutation was not reached, whereas those with the P53 mutation had a median progression-free survival of 22 months, which is still meaningful but still less than those who did not have a P53 mutation. Which again is not entirely unexpected. But the overall response rate of the combination of ibrutinib and venetoclax was very high at 90%, and the median duration of response was about 21 months. Now comparing this to the relapse/refractory cohort, in those without a P53 mutation, the progression-free survival of the combination of ibrutinib and venetoclax was about 47 months versus those who don't have the P53 mutation was about 21 months with an overall response rate of 80%. I think one takeaway looking at this comparison of the first-line and relapse/refractory setting is that patients seem to do very similar in terms of overall response rate and progression-free survival, whether they were in the first line or in the later lines of treatment if they had the P53 mutation, which says that the combination of ibrutinib and venetoclax is effective no matter which phase of the disease the patient might be in, indicating its overall activity and being strong. Dr. John Sweetenham: Yeah, I thought that was an interesting observation, actually, how similar the outcomes were in those two groups. Dr. Marc Braunstein: No, I agree. And I think although patients with TP53 mutations did comparatively worse than those without the mutation according to progression-free survival, overall response rate, or complete remission rates, they did seem to be similar whether a patient was in first-line or relapsed refractory if they were P53 mutant and were treated with this combination. So, I think we need further data in the first line, such as the data that's awaiting publication from the TRIANGLE study, which is examining upfront ibrutinib. But certainly, BTK inhibitors have significant activity in either the first line or the relapse setting of mantle cell lymphoma. Dr. John Sweetenham: Great. Thanks, Marc. Let's wind up with one more abstract, and this is Abstract 7053. It's a 7-year analysis of the so-called ECHELON-1 study. This was a study comparing the standard of care, ABVD, with the same regimen with bleomycin substituted by brentuximab vedotin for patients with previously untreated advanced-stage classical Hodgkin lymphoma. The study at the time it was originally reported, resulted in a significant practice change in the first-line therapy of Hodgkin's lymphoma. We now have mature follow-up. What are your take-homes from this study? Dr. Marc Braunstein: The ECHELON-1 study has certainly been a practice-changing clinical trial where, as you said, brentuximab with the backbone of AVD was compared to ABVD, which was the prior standard. And this was examined in newly diagnosed patients with classical Hodgkin lymphoma who were at advanced-stage, stage 3 or 4. The publication, first of the progression-free survival, and more recently, in the New England Journal of Medicine in 2022, where we saw the 6-year overall survival was 94% with the brentuximab-containing arm versus 89% in the control arm, established the brentuximab AVD, or otherwise called AAVD, as the standard of care in advanced stage newly diagnosed classical Hodgkin lymphoma. The current study is now reporting 7-year follow-up on about 1,300 randomized patients who were enrolled in this impressive study. Though at a median follow-up of 89 months now, the 7-year overall survival was quite similar, 94% versus 89%, again favoring the brentuximab-containing arm. In particular, this was driven by patients who had stage 4 disease or those patients who were aged less than 60 in subgroup analyses. So, what I take away from this abstract in the 7-year follow-up of the ECHELON-1 is that brentuximab with AVD remains the standard of care for previously untreated advanced-stage classical Hodgkin lymphoma. It is worth noting that the SWOG S1826 study that was presented at ASCO last year compared nivolumab with AVD compared to brentuximab AVD and did show a slight PFS advantage of 94% versus 86% with nivolumab AVD. Obviously, these were different studies with different patient populations enrolled, so we're really just cross-comparing different studies. But I think brentuximab AVD, given the survival benefit that is retained now at seven years in the current abstract, still remains the standard of care for advanced-stage classical Hodgkin lymphoma. The role of immune checkpoint inhibitors like nivolumab is making headway in terms of treating newly diagnosed patients as well. Dr. John Sweetenham: Yeah, thanks, Marc. I mean, one of the observations that I thought was of interest in this study was the outcome for patients who were PET-2 positive, when you compare AAVD and ABVD. It does seem as if even in those patients who are PET-2 positive, having had AAVD, they still apparently have a better outcome than those who received ABVD in that situation who were PET-2 positive. So, I think that's another interesting observation. I'm not quite sure what it means, except speaking to the overall superior efficacy of that regimen. Dr. Marc Braunstein: You make a great point, John, because it's worth noting that in ECHELON-1, a PET scan was done after cycle 2, but the study was not PET-adapted. So even if you had a positive PET, you continued for the full six cycles of treatment. But PET-2 status is often used in various studies of Hodgkin lymphoma to guide whether to give additional cycles or escalate therapy. So, I think the benefit of presenting those subgroups is that even if you were PET-2 positive, you still did better by continuing on the brentuximab-containing regimen. Dr. John Sweetenham: Yeah, exactly. I mean, the other important takeaway message, I think, is that the outcome for patients with advanced Hodgkin lymphoma seems to continue to steadily improve, which is great news and also really remarkable. And I'm excited to see there may be some additional data presented at one of the late-breaking abstracts in this year's meeting, so it will truly be interesting to see what that shows us as well. Dr. Marc Braunstein: Incredible. Dr. John Sweetenham: Well, Marc, as always, thank you for sharing your insights with us today on the ASCO Daily News Podcast. We look forward very much to hearing the updated data from these abstracts at the meeting. Dr. Marc Braunstein: As do I and thank you so much for inviting me again. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's guest: Dr. Marc Braunstein @docbraunstein Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Marc Braunstein: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp Speakers' Bureau: Janssen Oncology Research Funding (Institution): Janssen, Celgene/BMS

new york canada philadelphia medicine patients os trials ontario fda ash esa triangle abstract new england journal hodgkin cancer care sanofi aml btk asco glaxosmithkline optic abbvie echelon multiple myeloma pfs cml bcl ut southwestern tki novel approaches mfi asco annual meeting avd hematologic malignancies tkis tp53 cd38 p53 michael wang ibrutinib adaptive biotechnologies sympatico bcr abl transcript dr janssen oncology ponatinib

Zanubrutinib - FDA Approval, Efficacy & Safety Profile in CLL - Discussion with Dr. Shadman

Oncology Brothers

Play Episode Listen Later May 23, 2024 22:13

Join Rahul and Rohit Gosain, the Oncology Brothers, in this insightful podcast episode where they discuss the latest advancements in hematology and oncology. In this episode, they are joined by Dr. Mazyar Shadman from Fred Hutch Cancer Center to delve into the Sequoia and Alpine trials that led to the approval of Zanubrutinib in CLL. Key Points Discussed: • The Sequoia trial focused on Zanubrutinib in first-line CLL treatment, showcasing its superiority over traditional chemotherapy. • The Alpine study compared Zanubrutinib to Ibrutinib in relapsed/refractory settings, demonstrating Zanubrutinib's efficacy and safety profile. • Acalabrutinib and Zanubrutinib were indirectly compared in a post-analysis, shedding light on their differences. • Dr. Shadman provides insights on managing common side effects of Zanubrutinib, highlighting its improved tolerability. Tune in to this episode for a comprehensive discussion on Zanubrutinib in CLL, including trial outcomes, comparisons, and practical considerations for patient care. Stay informed with the Oncology Brothers as they navigate the evolving landscape of oncology treatments

Safety and Tolerability of Changing Covalent BTK Inhibitor Treatment in a Patient Intolerant to Ibrutinib or Acalabrutinib

ReachMD CME

Play Episode Listen Later May 14, 2024

CME credits: 0.50 Valid until: 14-05-2025 Claim your CME credit at https://reachmd.com/programs/cme/safety-and-tolerability-of-changing-covalent-btk-inhibitor-treatment-in-a-patient-intolerant-to-ibrutinib-or-acalabrutinib/24454/ Selection of Bruton's tyrosine kinase (BTK) inhibitor therapy in CLL patients requires recognizing key differences between first- and next-generation agents in terms of the safety profile and efficacy across all patient types, including patients with high-risk features. Newer BTK inhibitors with greater kinase selectivity have shown fewer off-target adverse effects and allowed patients to switch BTK inhibitors with continued clinical benefit, fewer recurrences, and lower severity.

safety patients treatments selection cme btk rmd intolerant bruton inhibitor cll covalent reachmd tolerability cme/ce ibrutinib oncology and hematology

Applying the Latest Evidence and NCCN Guideline Recommendations in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Play Episode Listen Later May 7, 2024 47:23

In this episode, Danielle M. Brander, MD; Deborah Stephens, DO; and Brian Hill, MD, PhD, discuss key aspects of the NCCN CLL guidelines and share strategies for applying these recommendations in your clinical practice to optimize treatment and outcomes. The greater discussion addresses:Optimal selection of therapy for treatment-naive CLL, including second-generation covalent BTK inhibitorsConsiderations in therapy selection for previously treated CLLNovel strategies for treating CLL Presenters:Danielle M. Brander, MDAssistant Professor of MedicineDivision of Hematologic Malignancies and Cellular TherapyDuke Cancer InstituteDurham, North CarolinaBrian Hill, MD, PhDDirector, Lymphoid Malignancies ProgramStaff Physician, Department of Hematology and Medical OncologyTaussig Cancer InstituteCleveland ClinicCleveland, OhioDeborah Stephens, DOAssociate ProfessorDirector of the CLL ProgramLineberger Comprehensive Cancer CenterUniversity of North CarolinaChapel Hill, North CarolinaContent based on a live and online CME program supported by educational grants from AstraZeneca; BeiGene, Ltd.; and Lilly.Link to full program including downloadable slides: https://bit.ly/49YxtSq

phd md recommendations guidelines optimal astrazeneca cme hematology cll brian hill chronic lymphocytic leukemia rituximab nccn hematologic malignancies ibrutinib nccn guidelines rituxan btki imbruvica small lymphocytic lymphoma

Amivantamab for NSCLC, Drug-Coated Balloon for ISR, Ibrutinib Oral Suspension, Epcoritamab for Follicular Lymphoma, Govorestat for Galactosemia, Obeticholic Acid for PBC, Biktarvy for HIV, Roluperidone for Schizophrenia

New FDA Approvals

Play Episode Listen Later Mar 4, 2024 11:53

Visit nascentmc.com/podcast for full show notes Visit learnamastyle.com for the free course on ChatGPT4 for medical writers and editors. - The FDA has approved amivantamab (Rybrevant) in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test. This approval converts the May 2021 accelerated approval of amivantamab to full approval. - The FDA approved the AGENT Drug-Coated Balloon (DCB) for treating in-stent restenosis in coronary artery disease patients, introducing the first drug-coated coronary balloon in the US. It uses a paclitaxel-coated catheter to deliver medication directly to the vessel wall, offering an alternative to traditional treatments and aiming to reduce recurrence risks. The approval was based on the AGENT IDE trial, demonstrating its effectiveness over uncoated balloon angioplasty in reducing lesion failure, with no significant adverse events reported. - The FDA approved an oral suspension form of ibrutinib (Imbruvica) for several conditions, including chronic lymphocytic leukemia and chronic graft versus host disease, addressing the needs of patients who have difficulty swallowing pills. This is the first oral suspension formulation of a Bruton's tyrosine kinase inhibitor, originally approved in 2013 for mantle cell lymphoma. The approval, granted to Johnson & Johnson and Pharmacyclics, aims to simplify treatment for patients challenged with pill-swallowing. - Epcoritamab-bysp (Epkinly) received FDA approval for treating adult patients with relapsed or refractory follicular lymphoma after at least two prior therapies, marking it as the first subcutaneously administered bispecific antibody for this condition. It works by targeting both CD3 on T cells and CD20 on B cells to induce cell death. Based on the EPCORE NHL-1 trial results, this approval extends its use beyond diffuse large B-cell lymphoma, with AbbVie and Genmab sharing commercial responsibilities. - The FDA granted priority review to the New Drug Application for govorestat (AT-007), a treatment for classic galactosemia, potentially the first of its kind if approved. Govorestat, an aldose reductase inhibitor, aims to reduce harmful galactitol levels, based on phase 3 study results among pediatric patients. Applied Therapeutics announced a PDUFA target action date of August 28, 2024, highlighting the urgent need for treatments in this area. - Obeticholic acid (Ocaliva) received FDA consideration for an expanded application to treat primary biliary cholangitis, building on its 2016 accelerated approval. It's designed for patients with or without cirrhosis, showing promise in post-marketing studies to confirm its clinical benefits. The review includes data from various studies and real-world evidence, with a PDUFA target date of October 15, 2024, aiming to address the needs of this autoimmune liver disease population. - The FDA approved Biktarvy for HIV patients with suppressed viral loads who exhibit M184V/I resistance, offering a new treatment option for those with specific resistance mutations. Biktarvy combines three therapies in a single tablet, based on successful 48-week study data. Manufactured by Gilead Sciences, this approval expands treatment possibilities for patients facing resistance challenges. - The FDA rejected Minerva Neurosciences' New Drug Application for roluperidone as a treatment for schizophrenia's negative symptoms, citing insufficient evidence from a single study and lack of comprehensive data. Despite showing promise in targeting specific brain receptors, the FDA's concerns highlight the need for more extensive research and data to confirm its effectiveness and safety. Minerva plans to engage with the FDA to address these issues.

drug fda hiv acid oral suspension balloon schizophrenia johnson johnson manufactured abbvie bruton egfr gilead sciences nsclc coated cd3 follicular lymphoma cd20 genmab ibrutinib pharmacyclics imbruvica pdufa applied therapeutics

CAR T cells plus ibrutinib in relapsed/refractory MCL; targeting SGF29 in AML; diffusion-limited oxygen release from stored blood

blood medical saga limited targeting oxygen cart cells oncology diffusion medical research stored hematology refractory relapsed ibrutinib

Play Episode Listen Later Feb 22, 2024 18:50

In this week's episode we'll discuss CAR T cells plus ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma. Next, we'll learn about a new SAGA for acute myeloid leukemia. Finally, we'll hear about new evidence that oxygen delivery to tissues can become diffusion-limited during perfusion with stored blood.

ASH 2023 CLL/Lymphoma Highlights – ALPINE, SEQUOIA, SWOG-S1826, POLARIX Update with Dr. Mazyar Shadman

Oncology Brothers

Play Episode Listen Later Dec 21, 2023 21:04

In discussion with Dr. Mazyar Shadman from the Fred Hutch Cancer Center, covering the Chronic Lymphocytic Leukemia and Lymphoma key practice changing/informing abstracts from American Society of Hematology (ASH) 2023 conference from Community Oncology perspective. We covered 4 important practice informing studies with Dr. Shadman: - ALPINE: Ph 3, Extended Follow-up Confirms Sustained Superior PFS of Zanubrutinib vs Ibrutinib for Treatment of R/R Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma - SEQUOIA: Ph 3, Broad Superiority of Zanubrutinib Over BR Across Multiple High-Risk Factors: Biomarker Subgroup Analysis in the Treatment-Naive Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) without del(17p) - SWOG S1826: Nivolumab-AVD Is Better Tolerated and Improves PFS Compared to Bv-AVD in Older Patients (Aged ≥60 Years) with Advanced Stage Hodgkin Lymphoma - POLARIX Update: Deciphering the Clinical Benefit of Pola-R-CHP versus R-CHOP in Different Genetic Subtypes Beyond Cell of Origin in the POLARIX Study

treatments origin american society alpine sequoia lymphoma chronic lymphocytic leukemia hematology ash ibrutinib shadman swog community oncology r chop

Episode 36. ASH 2023 Lymphoma Recap with Dr. Toby Eyre

Play Episode Listen Later Dec 20, 2023 50:59

In this episode, we review the hottest updates in lymphoma from the American Society of Hematology 2023 meeting with Dr Toby Eyre, a consultant haematologist at the University of Oxford in the UK. Here are the abstracts that were discussed: Mantle Cell Lymphoma 1. BOVen trial-A Multicenter Phase 2 Trial of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients with Treatment-Naïve, TP53-Mutant Mantle Cell Lymphoma https://ash.confex.com/ash/2023/webprogram/Paper180069.html 2. SYMPATICO Trial: Ibrutinib Combined with Venetoclax in Patients with Relapsed/Refractory Mantle Cell Lymphoma (Late Breaking Abstract) https://ash.confex.com/ash/2023/webprogram/Paper191921.html Chronic Lymphocytic Leukemia 1. FLAIR trial: Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease Link for simultaneous NEJM publication: https://www.nejm.org/doi/10.1056/NEJMoa2310063 2. Ibrutinib retreatment in Phase 2 CAPTIVATE study: https://ash.confex.com/ash/2023/webprogram/Paper187128.html Hodgkin Lymphoma 1. S1826 outcomes in older adults: https://ash.confex.com/ash/2023/webprogram/Paper180114.html Diffuse Large B-cell Lymphoma 1. Smart STOP study: Lenalidomide, Tafasitamab, Rituximab, and Acalabrutinib Alone and with Combination Chemotherapy for the Treatment of Newly Diagnosed Diffuse Large B-Cell Lymphoma https://ash.confex.com/ash/2023/webprogram/Paper180381.html 2. Mosunetuzumab and Polatuzumab Vedotin Demonstrates Preliminary Efficacy in Elderly Unfit/Frail Patients with Previously Untreated Diffuse Large B-Cell Lymphoma https://ash.confex.com/ash/2023/webprogram/Paper177588.html

A Year in Review and a Look to the Future: BTKi in CLL and MCL

professor shocking ohio state university kami withdrawal mcl hematology maddocks ibrutinib

Play Episode Listen Later Nov 20, 2023 27:33

In this episode, Ana Marin-Niebla, MD, PhD, and Stephan Stilgenbauer, MD, discuss key trial data on the use of BTK inhibitors in CLL and MCL throughout the past year, how these studies have impacted their practice, and what data they are looking forward to in the near future. The discussion includes analyses of: SHINE: First-Line Ibrutinib + Bendamustine/Rituximab Followed by Rituximab Maintenance in Older Patients With MCL TRIANGLE: Ibrutinib + Chemoimmunotherapy With or Without ASCT vs Chemoimmunotherapy Followed by ASCT in Younger Patients with Previously Untreated MCL ZUMA-2: Brexucabtagene Autoleucel in R/R MCL BRUIN: Pirtobrutinib for Previously Treated MCL GLOW: Fixed-Duration Ibrutinib + Venetoclax vs Chlorambucil + Obinutuzumab in Previously Untreated CLL FLAIR: Ibrutinib + Venetoclax vs FCR in Previously Untreated CLL ELEVATE-RR: Acalabrutinib vs Ibrutinib in Previously Treated CLL ALPINE: Zanubrutinib vs Ibrutinib in Previously Treated CLL BRUIN: Pirtobrutinib for Previously Treated CLLPresenters: Ana Marin-Niebla, MD, PhDHematology Consultant, Lymphoma UnitVall d'Hebron Institute of Oncology, Hematology DepartmentHospital Universitario Vall d'HebronBarcelona, SpainStephan Stilgenbauer, MDMedical Director Comprehensive Cancer Center UlmHead, Early Clinical Trials UnitHead, Division of CLL Dept. of Internal Medicine IIIUniversity Medical CenterUlm UniversityUlm, GermanyLink to full program: https://bit.ly/3MNaUri

phd md shine glow triangle alpine oncology btk bruin mcl carman tarmac cll chronic lymphocytic leukemia mantle cell lymphoma fcr ibrutinib asct btki

Kami Maddocks, MD, on the Shocking Ibrutinib Withdrawal

The HemOnc Pulse

Play Episode Listen Later Nov 16, 2023 31:52

In this episode of The HemOnc Pulse, Dr. Maddocks, Professor of Clinical Internal Medicine in the Division of Hematology at The Ohio State University, charts the treatment evolution of mantle cell lymphoma (MCL) from frontline therapy to future directions. She also explains her initial shock, and subsequent bittersweet reaction to the withdrawal of ibrutinib.

New Evidence With BTK Inhibitor Therapy in CLL and MCL From SOHO 2023

Play Episode Listen Later Oct 4, 2023 20:58

In this episode, Catherine C. Coombs, MD, MS, and Toby Eyre, MBChB, MD, discuss key trials presented at SOHO 2023 evaluating the use of BTK inhibitors in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The discussion includes analyses of: Matching-adjusted indirect comparison of 3 randomized phase III trials of ibrutinib for relapsed/refractory CLL Meta-analysis of cardiovascular adverse events with second-generation BTK inhibitors in CLL BRUIN: updated results of pirtobrutinib in covalent BTK inhibitor–pretreated MCLViPOR: venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide for relapsed/refractory and treatment-naive MCLPresenters:Catherine C. Coombs, MD, MSAssociate Clinical ProfessorDivision of Hematology/Oncology, Department of MedicineUCI HealthOrange, CaliforniaToby Eyre, MBChB, MDHonorary Senior LecturerHematology and CancerUniversity of OxfordConsultant HematologistDepartment of HematologyHematology and Cancer Centre, Oxford University Hospitals NHS Foundation TrustOxford, United Kingdom

ms united kingdom therapy md soho alpine resonate btk bruin mcl new evidence inhibitor cll hematology oncology mbchb cancer centre ibrutinib

Obinutuzumab, ibrutinib, and venetoclax in untreated CLL with deletion(17p)/TP53 mutation; NOTCH2 mutants promote chemo-resistance in DLBCL; and the role of DBY/HLA class II complexes in chronic GVHD

medical resistance chronic promote oncology mutation mutants chemo medical research complexes hematology untreated deletion gvhd class ii dlbcl tp53 ibrutinib

Play Episode Listen Later Sep 14, 2023 22:07

In this week's episode, we'll discuss the findings from the final analysis of the CLL2-GIVe trial, learn how NOTCH2 mutants promote resistance to chemotherapy in diffuse large B-cell lymphoma, and discuss the role of DBY/HLA class II complexes in chronic graft-versus-host disease.

Detailed safety profile of acalabrutinib vs ibrutinib in CLL, inflammation in trauma-induced coagulopathy, abatacept exposure and acute GVHD risk

trauma risk safety medical profile exposure inflammation detailed oncology acute induced medical research hematology gvhd hsct coagulopathy ibrutinib

Play Episode Listen Later Aug 24, 2023 20:56

In this week's episode, we'll review a detailed safety profile of acalabrutinib versus ibrutinib in patients with previously treated chronic lymphocytic leukemia, discuss a report that leukocyte inflammation contributes to trauma-induced coagulopathy by oxidation and degradation of fibrinogen, and finally, discuss a pharmacokinetic-pharmacodynamic analysis that shows higher abatacept exposure decreases occurrence of acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor.

New Evidence With BTK Inhibitor Therapy in MCL From ICML 2023

united kingdom therapy md btk bruin mcl new evidence inhibitor hematology oncology mbchb icml cancer centre ibrutinib

Play Episode Listen Later Aug 17, 2023 14:39

In this episode, Catherine C. Coombs, MD, and Toby Eyre, MBChB, MD, discuss key trials presented at ICML 2023 evaluating the use of BTK inhibitors in mantle cell lymphoma (MCL). The discussion includes analyses of: Phase II trial of acalabrutinib with rituximab for older patients with untreated MCL BRUIN: updated results of pirtobrutinib in covalent BTK inhibitor–pretreated MCL IMCL-2015 GELTAMO: 5-year update ibrutinib for untreated indolent MCL Presenters: Catherine C. Coombs, MD, MSAssociate Clinical ProfessorDivision of Hematology/Oncology, Department of MedicineUCI HealthOrange, CaliforniaToby Eyre, MBChB, MDHonorary Senior LecturerHematology and CancerUniversity of OxfordConsultant HematologistDepartment of HematologyHematology and Cancer Centre, Oxford University Hospitals NHS Foundation TrustOxford, United Kingdom

New Evidence With BTK Inhibitor Therapy in CLL From EHA 2023

ms united kingdom therapy md sequoia captivate btk new evidence inhibitor cll hematology oncology mbchb eha cancer centre ibrutinib

Play Episode Listen Later Jul 28, 2023 27:03

In this episode, Catherine C. Coombs, MD, MS, and Toby Eyre, MBChB, MD, discuss key trials presented at EHA 2023 evaluating the use of BTK inhibitors in chronic lymphocytic leukemia (CLL). The discussion includes analyses of:CLL12: final results of the phase III trial of ibrutinib vs placebo in asymptomatic, treatment-naive CLLSEQUOIA: extended follow-up of zanubrutinib vs BR in treatment-naive CLLCAPTIVATE: 4-year follow-up from the fixed duration cohort of ibrutinib plus venetoclax in CLL/small lymphocytic lymphomaPhase II trial of acalabrutinib plus obinutuzumab in treatment-naive CLLBRUIN: genomic evaluation of resistance to pirtobrutinib in BTK inhibitor‒pretreated CLLPresenters:Catherine C. Coombs, MD, MSAssociate Clinical ProfessorDivision of Hematology/Oncology, Department of MedicineUCI HealthOrange, CaliforniaToby Eyre, MBChB, MDHonorary Senior LecturerHematology and CancerUniversity of OxfordConsultant HematologistDepartment of HematologyHematology and Cancer Centre, Oxford University Hospitals NHS Foundation TrustOxford, United Kingdom

Dr. Matt Kalaycio on the Importance of GVHD Clinical Trials

Marrow Masters

Play Episode Listen Later Jun 22, 2023 28:00

Dr. Matt Kalaycio is the Vice Chairman of the Taussig Cancer Institute at the Cleveland Clinic. He joins us today to talk about clinical trials - the hope they bring, the lives they save, and why they are so important in regards to Graft Versus Host Disease.For example, the popular GVHD drugs Ruxolitinib, Ibrutinib, and Belumosudil They were found to be effective, thanks to clinical trials Dr. Kalaycio walks us through how that happened.Clinical trials are often intimidating, or even frightening to patients. People are afraid of being a "guinea pig." Dr Kalaycio addressed this and goes through all the safeguards around clinical trials, as well as the three phases of clinical trials.This may be hard to believe, but a long time ago, doctors would experiment on patients without their knowledge or consent. Thankfully those days are long behind us, and patients now give informed consent. Everything is explained to them, and all their questions are answered. Perhaps most importantly, the patient can opt out of the trial at any time for any reason.Many GVHD patients are offered the chance to participate in a clinical trial. If you'd like to learn more, the first place to start is with your treatment team. Beyond that, you can also visit the clinical trials website below.We close by asking Dr. Kalaycio about some of the clinical trials he's currently involved with, as well as what gives him hope going forward. He's been working with GVHD patients and their loved ones since 1992, and he's had a front row seat for just how far treatment has come. He is compassionate and empathetic and it shines through in this interview. Clinical Trials Website: https://clinicaltrials.gov/Cleveland Clinic Website: https://my.clevelandclinic.org/Dr. Matt Kalaycio bio: https://my.clevelandclinic.org/staff/473-matt-kalaycioOther ResourcesNational Bone Marrow Transplant Link - (800) LINK-BMT, or (800) 546-5268.nbmtLINK Website: https://www.nbmtlink.org/nbmtLINK Facebook Page: https://www.facebook.com/nbmtLINKnbmtLINK YouTube Page can be found by clicking here.Thank you to this season's sponsors:Supported by Pharmacyclics, an AbbVie Company (https://www.pharmacyclics.com/) and Janssen Biotech, Inc. (https://www.janssen.com/)Incyte: https://www.incyte.com/

clinical clinical trials vice chairman cleveland clinic phase one phase two phase three gvhd incyte ibrutinib pharmacyclics abbvie company

Episode 21. Newly Diagnosed Mantle Cell Lymphoma

cancer clinical triangle supplement mcl hematology rct newly diagnosed mantle cell lymphoma ibrutinib

Play Episode Listen Later May 3, 2023 46:05

In this episode, we delve into the management of newly diagnosed mantle cell lymphoma with Dr. Martin Dreyling. Here the shownotes:2:11 How to diagnose mantle cell lymphoma (MCL)?6:51 Clinical manifestations of mantle cell lymphoma7:52 How to manage leukemic variant of MCL? 12:08 Is Watch-and-Wait reasonable in selected cases of nodal MCL with low Ki-67?17:21 Overview on treatment of newly diagnosed MCL19:03 Are all cytarabine-based regimens for MCL created equally? RCT of Autologous Transplantation in MCL: https://pubmed.ncbi.nlm.nih.gov/15591112/21:39 In a world without upfront ibrutinib access as per TRIANGLE trial, do all fit patients with MCL need consolidation with auto-transplant? 22:44 How to approach unfit patients with newly diagnosed MCL? RCT of bortezomib-based therapy (VR-CAP) in newly diagnosed MCL: https://pubmed.ncbi.nlm.nih.gov/25738670/24:57 SHINE Trial-RCT of Ibrutinib plus BR in newly diagnosed MCL: https://pubmed.ncbi.nlm.nih.gov/35657079/30:38 TRIANGLE Trial-RCT of upfront ibrutinib with or without auto-transplant in newly diagnosed MCL:https://ashpublications.org/blood/article/134/Supplement_1/2816/42350443:01: Does Allo-Transplant have any role in MCL?44:08: What are the likely next breakthroughs in newly diagnosed MCL space?

JACC: CardioOncology – Ibrutinib Results in Increased Risk of Atrial Fibrillation and Major Bleeding in Older CLL Patients

JACC Speciality Journals

Play Episode Listen Later Apr 18, 2023 3:46

Commentary by Dr. Shazia Nakhoda

patients commentary older bleeding atrial fibrillation increased risk jacc ibrutinib

Chronic Lymphocytic Leukemia | Oncology Today with Dr Neil Love: Key Presentations from the 64th American Society of Hematology (ASH) Annual Meeting — Chronic Lymphocytic Leukemia Edition

Research To Practice | Oncology Videos

Play Episode Listen Later Apr 12, 2023 79:34

Featuring an interview with Dr John Allan, including the following topics: • Update on key studies of acalabrutinib in the front-line setting (0:00) • Updated data from the GLOW study: First-line fixed-duration ibrutinib and venetoclax compared to chlorambucil and Obinutuzumab (21:11) • Treatment outcomes after achieving undetectable minimal residual disease (MRD) with first-line ibrutinib and venetoclax: Updated analysis of the CAPTIVATE trial (35:06) • Ibrutinib/venetoclax with MRD-driven duration of treatment: Updated analysis of the FLAIR trial (48:08) • Acalabrutinib with venetoclax and obinutuzumab for previously untreated chronic lymphocytic leukemia (CLL) in a population enriched for high-risk disease (50:49) • Risk factors to predict failure of therapy using fixed-duration venetoclax/obinutuzumab (53:22) • Updates on the ALPINE and BRUIN studies of zanubrutinib and pirtobrutinib, respectively, for relapsed/refractory CLL (56:15) • Emerging data with novel Bcl-2 inhibitors (1:11:26) • Evolving data with subcutaneous epcoritamab for patients with Richter's transformation and CLL (1:14:37) CME information and select publications

BTK-Inhibitor Development: A Researcher's Perspective

Healthcare Unfiltered

Play Episode Listen Later Feb 7, 2023 55:16

Few drugs in oncology have transformed the way we take care of patients. Ibrutinib is one such drug, and it belongs to a class called "BTK inhibitors" In this episode, Chadi captures the story of developing the drug through the eyes of Dr. Jeff Sharman, a prolific investigator and researcher; he is the director of research at the Willamette Valley Cancer Institute as well as the medical director of hematology research for The US Oncology Network. Dr. Sharman begins by discussing the dynamics of opening clinical trials throughout the US Oncology Network, then shares his career choice to move into the community setting, how a research idea he came up with led him down a path of being discouraged by the academic research world, his experience treating the first ever patient in the world with ibrutinib, and the underpinnings of the biotech world. More on his story and the drug development dynamics are described in the fascinating book "For Blood and Money," authored by Nathan Vardi, who is next week's guest. These two back-to-back episodes will make you think, pause, and reflect. Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on Youtube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

money development researchers btk inhibitor sharman chadi ibrutinib for blood

5.34 - ASH Update #2 - ALPINE - Zanibrutinib vs Ibrutinib - Deconstructed

Plenary Session

Play Episode Listen Later Dec 24, 2022 21:37

Sample size games, primary endpoint, head to head trials in oncology Rate this podcast on itunes Coming next is Triangle trial

health medicine policy triangle alpine oncology deconstructed ibrutinib

Episode 11. ASH22 Recap: Lymphoma and CLL

study cancer patients phase population lymphoma hematology rct asymptomatic cll mantle cell lymphoma ibrutinib

Play Episode Listen Later Dec 21, 2022 39:02

ALPINE Trial: Zanubrutinib vs Ibrutinib in Relapsed/Refractory CLL (https://www.nejm.org/doi/full/10.1056/NEJMoa2211582) CLL2-Give Trial: Updated results Obinutuzumab (G), Ibrutinib (I), and Venetoclax (Ve) triplet in Untreated Patients with CLL with 17p Deletion/TP53 Mutation (https://ash.confex.com/ash/2022/webprogram/Paper163245.html) AVO Trial: Acalabrutinib, Venetoclax, Obinutuzumab (AVO) in a Population of Previously Untreated Patients with CLL Enriched for High-Risk Disease (https://ash.confex.com/ash/2022/webprogram/Paper168003.html) Watch-and-Wait RCT in Follicular Lymphoma: Long-term follow-up of Phase 3 Study of Rituximab Versus a Watch and Wait Approach for Patients with Asymptomatic, Low Tumour Burden Follicular Lymphoma (https://ash.confex.com/ash/2022/webprogram/Paper156790.html) Augment Trial: Update of Phase 3 RCT comparing Rituximab-Revlimid (R2) vs Rituximab-Placebo in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (https://ash.confex.com/ash/2022/webprogram/Paper158631.html) TRIANGLE Study: Ibrutinib Combined with Standard First-Line Treatment or As Substitute for Autologous Stem Cell Transplantation in Younger Patients with Mantle Cell Lymphoma (https://ash.confex.com/ash/2022/webprogram/Paper163018.html)

Evolving Role of BTK Inhibitors in CLL: Experts Answer Your Questions

Play Episode Listen Later Nov 9, 2022 10:33

In this episode, Farrukh T. Awan, MD, and Nicole Lamanna, MD, answer questions from an audience of healthcare professionals on topics related to the use of BTK inhibitors for the management of chronic lymphocytic leukemia (CLL). The topics covered include:Whether it is justifiable to use chlorambucil plus obinutuzumab as a control arm in a registrational trial todayRelevance of overall response rate vs progression-free survival for BTK inhibitor therapyApproval of ibrutinib/venetoclax combination therapy for patients with CLLKey differences between zanubrutinib and acalabrutinib in the treatment of patients with CLLHow to transition/overlap next therapy in patients with CLL with progression while receiving a BTK inhibitorFaculty:Farrukh T. Awan, MDAssociate Professor of Internal MedicineDirector of Lymphoid Malignancies ProgramHarold C. Simmons Comprehensive Cancer CenterUniversity of Texas Southwestern Medical CenterDallas, TexasNicole Lamanna, MDAssociate ProfessorLeukemia ServiceDirector of CLL ProgramHematologic Malignancies SectionDepartment of MedicineNew York-Presbyterian/Columbia University Medical CenterNew York, New YorkLink to the complete program, including downloadable slidesets and an on-demand webcast:https://bit.ly/3EjvSKm

md btk mrd inhibitors evolving role awan cll rituximab fcr ibrutinib nicole lamanna

New Evidence With BTK Inhibitor Therapy in CLL and MCL From the SOHO 2022 Annual Meeting

Play Episode Listen Later Oct 28, 2022 21:46

In this episode, Christopher R. Flowers, MD, MS, and Kami Maddocks, MD, discuss their choices of recent important trials presented at the Society of Hematologic Oncology 2022 Annual Meeting evaluating the use of BTK inhibitors in chronic lymphocytic leukemia and mantle cell lymphoma. The discussion includes analyses of:GLOW: phase III randomized trial of ibrutinib plus venetoclax vs chlorambucil plus obinutuzumab for older or unfit patients with previously untreated chronic lymphocytic leukemia BRUIN: phase I/II study of pirtobrutinib for previously treated mantle cell lymphoma (including previous BTK inhibitor)Presenters:Christopher R. Flowers, MD, MSDepartment Chair, Department of Lymphoma/MyelomaDivision of Cancer MedicineUniversity of Texas MD Anderson Cancer Center Houston, TexasKami Maddocks, MDProfessor of Clinical Internal MedicineDivision of Internal MedicineDepartment of HematologyThe Ohio State UniversityLymphoma Program DirectorThe Ohio State University James Cancer HospitalColumbus, Ohio

society ms ohio therapy md shine glow triangle soho annual meetings btk bruin mcl new evidence inhibitor mantle cell lymphoma ibrutinib mdprofessor

Lineage switching in MLL/AF4 leukemia, ibrutinib in mantle cell lymphoma with CNS relapse, and gilteritinib plus azacitidine in newly diagnosed FLT3-mutated AML

medical switching oncology leukemia lineage relapse medical research aml hematology mutated newly diagnosed mantle cell lymphoma flt3 ibrutinib

Play Episode Listen Later Oct 27, 2022 22:58

In this week's episode we'll discuss the role of epigenetic regulator genes in lineage switching in MLL/AF4 leukemia, learn more about the efficacy of ibrutinib in mantle cell lymphoma with central nervous system relapse, and discuss the findings from a phase 3 trial of gilteritinib plus azacitidine in patients with newly diagnosed FLT3-mutated AML.

Episode 8. Management of Newly Diagnosed CLL

FDA Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)

Play Episode Listen Later Oct 26, 2022 62:40

Key articles and trials discussed in the episode:1. Excellent review in NEJM on treatment of CLL (2020): https://www.nejm.org/doi/full/10.1056/NEJMra19082132. Alliance Trial (Ibrutinib vs chemoimmunotherapy in older patients with untreated CLL): https://www.nejm.org/doi/full/10.1056/NEJMoa18128363. E1912 (Ibrutinib vs chemoimmunotherapy in younger/fit patients with CLL): https://www.nejm.org/doi/full/10.1056/NEJMoa18170734. RCT testing Acalabrutinib vs Ibrutinib (non-inferiority) in relapsed CLL: https://ascopubs.org/doi/10.1200/JCO.21.012105. ELEVATE-TN Study (Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab): https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30262-2/fulltext6. CLL-11 trial (showed that obinutuzumab>rituximab in CLL): https://www.nejm.org/doi/full/10.1056/nejmoa13139847. Initial data from German CLL-13 trial: https://ashpublications.org/blood/article/138/Supplement%201/71/477548/A-Randomized-Phase-III-Study-of-Venetoclax-Based8. Ventricular arrhythmia and sudden death with BTK inhibitor: https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2022016953/486090/Ventricular-Arrhythmias-and-Sudden-Death-Events?redirectedFrom=fulltext9. CLL14 trial (venetoclax-obinutuzumab in untreated CLL): https://www.nejm.org/doi/full/10.1056/nejmoa181528110. Extended follow-up and MRD dynamics in CLL14 trial: https://ascopubs.org/doi/10.1200/JCO.21.0118111. CAPTIVATE Study on fixed-duration Ibrutinib-venetoclax in newly diagnosed CLL: https://ashpublications.org/blood/article/139/22/3278/484114/Fixed-duration-ibrutinib-plus-venetoclax-for-first12. Ibrutinib-Venetoclax for treatment of CLL: https://www.nejm.org/doi/full/10.1056/nejmoa190057413. GLOW study (Ibrutinib-Venetoclax vs Chlorambucil-Obinutuzumab): https://evidence.nejm.org/doi/abs/10.1056/EVIDoa2200006

management cancer glow initial supplement extended btk mrd hematology rct nejm piis0140 cll newly diagnosed ventricular redirectedfrom jco ibrutinib

FDA D.I.S.C.O. Burst Edition: FDA approvals of Imbruvica (ibrutinib) for pediatric patients with chronic graft versus host disease, and Pemazyre (pemigatinib) for adults with relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement

Play Episode Listen Later Sep 28, 2022 5:59

Listen to a soundcast of the 8/24/22 and 8/26/22 FDA approvals of Imbruvica (ibrutinib) for pediatric patients with chronic graft versus host disease, including a new oral suspension, and Pemazyre (pemigatinib) for relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement.”

fda adults chronic disc burst graft approvals refractory relapsed pediatric patients host disease myeloid ibrutinib rearrangement lymphoid imbruvica fgfr1

2022 Research Round Up: Lung Cancer, Lymphoma, and Childhood Cancers

Cancer.Net Podcasts

Play Episode Listen Later Sep 15, 2022 30:09

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 voice of the world's oncology professionals. 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. Guests' statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In the Research Round Up series, ASCO experts and members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today's episode, our guests will discuss new research in lung cancer, lymphoma, and childhood cancer that was presented at the 2022 ASCO Annual Meeting, held June 3-7 in Chicago, Illinois. First, Dr. Charu Aggarwal will discuss 3 studies looking at treatment options for people with non-small cell lung cancer. Dr. Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the Cancer.Net Associate Editor for Lung Cancer. You can view Dr. Aggarwal's disclosures at Cancer.Net. Dr. Aggarwal: Hello and welcome to this Cancer.Net podcast. I'm bringing you updates from the Annual Meeting of the American Society of Clinical Oncology, held in Chicago in 2022. I'm Dr. Charu Aggarwal. I'm the Leslye Heisler Associate Professor for Lung Cancer Excellence at the University of Pennsylvania's Abramson Cancer Center. I will be discussing updates on 3 studies today that offer insights and new advances in the management of patients with non-small cell lung cancer. I don't have any direct relationship with any of these companies or studies, and you can view a list of my disclosures on the Cancer.Net website. First off, I would like to talk a little bit about advances in the management of patients with EGFR exon 20 mutations. We know that a lot of advances have been made in the management of patients with non-small cell lung cancer, and much of that has been attributed to the fact that we are now able to deliver targeted therapy for a subset of patients. EGFR mutations form one such subset where we have a lot of oral drugs that are available, and we can offer these that improve survival, and patients can avoid chemotherapy, immunotherapy, and other IV infusional therapies. Within the subset of EGFR mutations lies this unique subset of EGFR exon 20 insertion mutations, which have been historically harder to target with currently available EGFR inhibitors. And over the last 5 years, we have seen tremendous growth of opportunities, targets, and new drugs for this subset of patients. The mutations in this subset forms about 2% to 5% of all non-small cell lung cancers. But now we have 2 FDA-approved drugs in this space, one being intravenously administered, amivantamab, and another that is orally available, mobocertinib. We covered this in a podcast as well as a blog, so please check those out on our Cancer.Net website. But building upon that progress, there is now another drug that was reported at ASCO. This drug is called CLN-081. And we saw preliminary activity in a phase 1 and 2 study of this molecule or this drug in patients with EGFR exon 20 insertion mutations. It's an orally available drug. The top line data is that it is safe, it is effective, it was tested in different doses. It was tested at less than 65 milligrams, 100 milligrams, and 150 milligrams, again, as I mentioned, administered orally, and we saw responses and patients that had previously received other therapies and may have progressed on other therapies. And what we found was that this drug also tends to have activity against brain metastases, which I think is this huge unmet need in the management of such patients. So I think more to come, but again, I think offers us an insight into what may be in the future, an attractive drug for our patients with EGFR exon 20 insertion mutations. So stay tuned, more on that in the future. Shifting gears, I would like to now talk about one of the common mutations. So we talked about EGFR exon 20, which is about only 2% to 5%, but the largest subset of mutations in non-small cell lung cancer really revolves around KRAS mutations, and these form about 30% to 35% of all mutations in non-squamous, non-small cell lung cancer. And amongst this group there is another subset which is KRAS G12C non-small cell lung cancer, that forms about 13% of all lung cancers. We have 1 approved drug already in this space by the name of sotorasib that is FDA approved for the management of patients with this particular mutation after having received 1 prior therapy, be it chemo-immunotherapy or immunotherapy. At this year's ASCO meeting, we heard data from a study called KRYSTAL-1, which looked at the activity and safety of another molecule called adagrasib, which is an orally available drug targeting KRAS G12C, again, in a similar population of patients with advanced and metastatic non-small cell lung cancer harboring a mutation. We found that this drug is again effective, the overall response rate was about 43%, the majority of the patients had stabilization of disease, about 80%, and many patients were able to remain on treatment with stabilization of disease. We found that this drug does have side effects and adverse events and most commonly of this were diarrhea, nausea, vomiting, and fatigue. Many patients did require dose reductions, but the activity of the drug remained despite dose reductions. Now, what would be the advantage of this drug against the currently available sotorasib? In another smaller study reported at ASCO, there seemed to be activity in the brain, including intracranial penetration with the use of this molecule, adagrasib, which has not been demonstrated before with other KRAS G12C inhibitors, so I think that makes it a potentially attractive option. Again, I will say that the report of this intracranial activity was in a very small subgroup of patients, so I think needs to be further corroborated in a larger study. Shifting gears again and talking about our last study, so I would like to highlight what do we do if, in case, patients don't have a targetable mutation. I want to highlight that we do have a lot of available options, and we are continuing to improve upon available options. The way we treat such patients is by using immunotherapy, either alone or in combination with chemotherapy. But what do we do after this treatment stops working? Researchers from the Southwestern Oncology Group, or SWOG, launched a massive national effort called Lung-MAP, which is basically a clinical trial that evaluates several different strategies all at once, either for patients with targetable mutations or for patients without a targetable alteration. And they reported results from a study that evaluated the combination of pembrolizumab with ramucirumab in patients that may have progressed after frontline immunotherapy. Now, pembrolizumab is immunotherapy, so the concept was, can we continue immunotherapy beyond progression and perhaps get some synergistic activity by using ramucirumab, which is a drug that prevents blood vessels from forming in the tumor itself. It's an anti-angiogenic agent, meaning that it is a targeted molecule that prevents blood vessel formation and promotes tumor death. What they found was that patients that received pembrolizumab and ramucirumab were more likely to live longer, so overall survival was longer for patients with this combination compared to a physician investigator discretion choice, such as chemotherapy in combination with ramucirumab or other chemotherapies that are otherwise used in the second line setting. And interestingly, we did not find a significant improvement in shrinkage with this combination of pembrolizumab and ramucirumab or a significant reduction in the time of progression-- or, sorry, prolongation of the time of progression of disease. But the overall survival findings are interesting, and I think that's why we are including them in this podcast because that's one of the approaches that is leading to an improvement in survival and improvement in outcomes. I will point out that this is a phase 2 study. These results would need to be validated in a large prospective phase 3 trial so that we can account for certain confounding factors that may have led to these results. Having said that, I think there's a tremendous excitement, there's tremendous excitement in this field. I gave you examples of, or highlighted, 3 studies: one in patients with EGFR exon 20 insertion mutations, another in KRAS G12C mutations, and the third in patients who may have already received either immunotherapy or chemoimmunotherapy. We will continue to update our Cancer.Net website with updates as they come through, new advances, new studies, so thanks for following, thanks for listening, and more to come. Stay tuned. Thank you. ASCO: Thank you, Dr. Aggarwal. Next, Dr. Christopher Flowers will discuss new research in treating people with different subtypes of lymphoma, including mantle cell lymphoma and diffuse large B-cell lymphoma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and was appointed Division Head ad interim of Cancer Medicine in August 2020. He is also the 2022 Cancer.Net Associate Editor for Lymphoma. You can view Dr. Flowers' disclosures at Cancer.Net. Dr. Flowers: Hello and welcome to this podcast that is a review of late breaking abstracts from the ASCO Meeting and recent updates in lymphoma. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and Interim Division Head for Cancer Medicine at The University of Texas MD Anderson. And it's my great pleasure to discuss with you some of these late breaking abstracts. I do have some disclosures that are related to the content that I will present from this year's ASCO Meeting and recent studies in lymphomas. Those are available at Cancer.Net. Those relate to my role as a consultant for the development of clinical trials in lymphomas and research funding that MD Anderson has received from companies related to my role in clinical trials in lymphoma and clinical trials across cancers. So, the ASCO Meeting had a host of new information that was presented. Some of that information centers around key clinical trials. One that was a pivotal clinical trial, the SHINE clinical trial, looked at patients with mantle cell lymphoma, a rarer lymphoma subtype, that looked at the combination of bendamustine and rituximab, a standard chemoimmunotherapy combination, compared to that same chemoimmunotherapy combination, bendamustine, rituximab, plus the Bruton's tyrosine kinase inhibitor ibrutinib. Ibrutinib, as some of you may know, is a kind of therapy that is typically used in the relapse setting for patients with mantle cell lymphoma when they have their disease come back. And the SHINE clinical trial was looking at adding it to frontline therapy. What this randomized, controlled trial in the phase 3 setting found was that patients who received the combination of bendamustine, rituximab, plus ibrutinib had improvement in their progression-free survival, meaning that the time that it took for their disease to come back or them to have deaths related to the lymphoma was longer for patients who received this combination. About 2.3 years longer than the group that received bendamustine, rituximab, plus placebo. And in total, that led to a median progression-free survival of 6.7 years. That study has now been published in the New England Journal of Medicine and was led by my colleague Dr. Michael Wong from MD Anderson. Dr. Wong also led another study that was presented at the ASCO Meeting looking at CAR T-cell therapy for patients with mantle cell lymphoma. That study has now been published in the Journal of Clinical Oncology, and it looks at brexucabtagene autoleucel, a kind of CAR T-cell therapy, where that-- the CAR T-cell therapy was successfully manufactured for 71 of the 74 patients in the trial. 68 of those patients received an infusion and the median progression-free survival, so the average amount of time that it took for patients to have progression of their disease, was about 25 months. And so a marked benefit for those patients who were receiving CAR T-cell therapy when their mantle cell lymphoma came back. There also were major breaking abstracts at the ASCO Meeting in the area of diffuse large B-cell lymphoma. As many of you may know, diffuse large B-cell lymphoma is the most common type of lymphoma that occurs in the United States. And there was a breaking trial that was presented in December at the American Society of Hematology Meeting describing polatuzumab, a CD79b antibody drug conjugate, as a new drug in the substitution of frontline therapy for patients with diffuse large B-cell lymphoma in combinations with rituximab, cyclophosphamide, adriamycin, and prednisone, or the pola-R-CHP arm, that compared favorably to rituximab and CHOP chemotherapy, which has been the standard of care for patients with diffuse large B-cell lymphoma. And that trial showed an improvement in progression-free survival. At this year's ASCO Meeting, Franck Morschhauser presented results from looking at subsets of that patient population. Those patients who had BCL2 by immunohistochemistry that was positive or MYC expression by immunohistochemistry that was positive, or both of those, what we call double-expressor lymphomas, those who have poorer risk than standard groups. And those double-expressor lymphomas, treated with pola-R-CHP, had improvement in progression-free survival compared to R-CHOP with a hazard ratio of 0.64 in that group. We also saw in a multitude of analysis that that supported the benefit of pola-R-CHP in patients with both BCL2-positive and MYC-positive diffuse large B-cell lymphoma. Another area that has been very hot in diffuse large B-cell lymphoma clinical trials is the role of bispecific antibodies. Bispecific antibodies are antibodies that bind both to CD20, a marker on the diffuse large B-cell or the lymphoma cells, and to the marker CD3, which is a marker on T-cells which brings the normal T-cells of the immune system in close proximity to the lymphoma cells and then leads to immune-directed killing of lymphoma cells. The agent glofitamab is an agent that was presented by Michael Dickinson at this year's ASCO Meeting in an abstract. And in this study, 107 patients who received more than 1 dose of steady treatment went on to have complete responses in about 35% of patients. And this showed that glofitamab induced durable complete responses and had a very favorable safety profile in patients with relapsed and refractory diffuse large B-cell lymphoma. And in this trial, they compared that also for patients who had prior exposure to CAR T-cells and showed that responses were also good in those patients. Another set of studies has also looked at bispecific antibodies and a whole host of other areas with multitude of other agents. Another study that was presented at this year's ASCO Meeting explored the use of bispecific antibodies in the frontline setting in combination with the R-CHOP regimen that I just discussed. In that study, Lorenzo Falchi presented results of the subcutaneous bispecific antibody epcoritamab in combination with R-CHOP. This was a relatively small study of 33 patients that showed that the combination of epcoritamab plus R-CHOP was something that was safe and tolerable. There were no new treatment emergent adverse events that led to discontinuation of epcoritamab in the study. And there are some adverse events that are of special interest that we see with the bispecific antibodies, and those include the kind of immune-mediated adverse events that we can also see with CAR T-cells, like cytokine release syndrome, or CRS, or neurologic toxicities that we can see there that are also called ICANS. What we've seen in this trial, that about 42% of patients had some form of cytokine release syndrome, but that most severe form of cytokine release syndrome, those that were greater than grade 3 in severity, was only in 3% of patients. And likewise, the neurologic toxicities, or ICANS, that were grade 2 was in only 3% of patients. Relatively few patients completed all therapy by the time that this was presented. Only 10 patients had completed 6 cycles of therapy, but that showed an overall response rate that was quite high in that patient population. There were a whole host of other trials that were presented at this year's ASCO Meeting, and those portend improved kinds of outcomes on the horizon for patients with lymphomas across the spectrum. And I think it's an exciting time moving forward for clinical trials in lymphoma and hopefully, to see new therapies that emerge for the management of this disease. One of those new therapies that happened outside of the ASCO Meeting was the recent FDA approval of CAR T-cell therapy in the relapse setting for follicular lymphoma. And this was based on the ELARA clinical trial. And I think the future is quite bright for therapies and for patients with lymphomas broadly. ASCO: Thank you, Dr. Flowers. Finally, Dr. Daniel Mulrooney will discuss new research in childhood cancers, including a study comparing treatment options for Ewing sarcoma, and several studies on neuroblastoma. Dr. Mulrooney is an Associate Member in the Division of Cancer Survivorship at St. Jude Children's Research Hospital. He is also the Cancer.Net Associate Editor for Pediatric Cancers. You can view Dr. Mulrooney's disclosures at Cancer.Net. Dr. Mulrooney: My name is Dr. Dan Mulrooney from St. Jude Children's Research Hospital. I'm the Deputy Director of the After Completion of Therapy Clinic at St. Jude and primary care for survivors of pediatric solid tumors. The annual ASCO Meeting is typically quite busy and full of research presentations sharing knowledge and advances in cancer treatment and care. Today, I'd like to highlight some of the exciting presentations in pediatric cancer. Please note, I do not have any relationships to disclose related to any of these studies. At this year's meeting, one of the highlights was a European study in patients with relapsed or refractory Ewing sarcoma. Ewing sarcoma is a rare bone cancer that typically occurs in adolescents or young adults. While challenging to treat, it is difficult to cure in patients who have relapsed, and studies are needed to improve the care of these patients. Investigators from 13 European countries and Australia and New Zealand studied the most common relapsed therapies, which include irinotecan and temozolomide, gemcitabine and docetaxel, topotecan and cyclophosphamide, or high-dose ifosfamide. The study enrolled 451 patients between 2014 and 2021 and randomly assigned them to one of these four treatments. Based on response rates, the first 2 arms were dropped and the study was largely a comparison between topotecan cyclophosphamide and high-dose ifosfamide. The main outcome was event-free survival. Event-free survival is a common way in a clinical trial to see how well a treatment works. It measures the time from treatment that the patient remains free of complications, such as return or progression of the cancer. But investigators also looked at overall survival, toxicity, and quality of life. The 6-month event-free survival was better for high-dose ifosfamide at 47% compared to 37% for topotecan cyclophosphamide. The median overall survival was also better for high-dose ifosfamide compared to topotecan cyclophosphamide. The results were best for children younger than 14 years old versus those 14 or greater. Toxicities included fever and neutropenia, nausea, vomiting, and diarrhea. Patients receiving high-dose ifosfamide had more neurologic and kidney toxicities, which might be expected since ifosfamide is known to affect these organ systems, while only descriptive measurements of quality of life appeared higher for those children treated with high-dose ifosfamide compared to topotecan and cyclophosphamide. The strength of this trial is its large size, particularly for a rare cancer, and the fact that it randomized patients to the most commonly used treatment regimens for relapsed Ewing sarcoma. Importantly, data did not previously exist comparing these different treatments. While the results of this study are promising, clearly more needs to be done, and there was a lot of discussion at the ASCO Meeting about how to further improve survival in these patients. This study provides some information for doctors and patients, but importantly, provides data to advance future trials, which will concentrate on incorporating new targeted drugs with high-dose ifosfamide. This study is ongoing and is adding additional arms to continue to improve the outcomes for patients with relapsed or refractory Ewing sarcoma. In addition to this study in Ewing sarcoma, several studies investigating neuroblastoma were presented. Neuroblastoma is the most common extracranial solid tumor in children and for children with high-risk disease requires intensive and prolonged treatment, including chemotherapy, surgery, radiation therapy, and stem cell transplantation. Treatment for these patients has improved since the introduction of immunotherapy, particularly an antibody directed at a particular antigen named GD2 on the neuroblastoma cells. One study showed improvement in outcomes using this antibody for children with relapsed or refractory neuroblastoma, and another study demonstrated feasibility of using this antibody earlier in treatment, which was not previously known to be safe and tolerable. In what is called the BEACON study, investigators tested whether the antibody, called dinutuximab, would be effective when combined with chemotherapy for relapsed or refractory neuroblastoma. They enrolled 65 patients from 2019 to 2021 and randomized these patients to either chemotherapy alone or chemotherapy plus dinutuximab. The median age of these children was 4 years. The overall response rate, which means either a complete or partial response, was 18% for the chemotherapy-only arm but improved to nearly 35% for those treated with chemotherapy and dinutuximab. The progression-free survival was 27% for chemotherapy only and improved to 57% for those treated with chemotherapy and the antibody. There was no change in overall survival, though investigators think this may have been due to some patients who had progressive disease and crossed over to the antibody arm of the study. This presentation was followed by a study from the Children's Oncology Group, which investigated the feasibility of adding antibody treatment earlier in the treatment regimen for neuroblastoma. Prior studies had used antibody later in treatment when the tumor burden is thought to be lower. The endpoint of this study was tolerability measured by toxic deaths or unacceptable toxicities, such as adverse reactions to the medication. For example, sustained low blood pressure requiring a ventilator or breathing machine, or severe neuropathy. 42 high-risk neuroblastoma patients were enrolled from 8 different children's hospitals between 2019 and 2021. 41 of the 42 were able to complete the induction chemotherapy plus the antibody. There were no toxic deaths or unacceptable toxicities. Importantly, 85% were able to complete the next phase of treatment, called the consolidation phase, and 79% were able to complete the following phase after consolidation, called post-consolidation. One-year event-free survival was 83%, and 1-year overall survival was 95%. Now, it's important to know these are still early results, and the trial recently closed, and some of the patients have only completed therapy within the last year. Both of these studies add to the knowledge of chemoimmunotherapy for children with high-risk neuroblastoma. These studies provide a foundation for larger randomized trials that will further advance the care of these children. And finally, another study looked at race, ethnic, and socioeconomic disparities among children treated for high-risk neuroblastoma on Children's Oncology Group studies. There were no differences in event-free survival, but there were differences in overall survival based on ethnicity. The 5-year survival was lowest for Hispanic patients at 47%, 50% for non-Hispanic other ethnicities, which included Asian, Native American, Native Hawaiian, or Pacific Islanders, and 62% for non-Hispanic Black and non-Hispanic White children. Importantly, these investigators also studied household and neighborhood poverty. Overall, survival was lower for children living in poverty, though some of these differences went away when accounting for other factors, such as stage of disease or high-risk features. This study is important because it highlights the increasing need to collect data on clinical trials that may contribute to inequities in outcomes. While most studies collect data on the race and ethnicity of participants, other factors known as social determinants of health, such as income, neighborhood, education, access to health care, and insurance coverage, may also contribute to outcomes in pediatric cancer patients. Overall, the studies highlighted here and presented at this year's ASCO Annual Meeting focused on difficult-to-treat cancers, such as relapse or refractory disease, and they have laid the groundwork for future investigations to continue to improve survival rates for all children diagnosed with a malignancy through improved therapies and by addressing potential social barriers. Thank you for listening to this brief summary of the new research in pediatric oncology presented at the 2022 ASCO Annual Meeting. ASCO: Thank you, Dr. Mulrooney. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

united states university children chicago australia european philadelphia medicine new zealand pennsylvania event cancer illinois asian journal patients treatments shifting shine native americans flowers fda iv researchers hispanic conquer wong deputy director toxicity cart american society investigators beacon chop annual meetings ewing pacific islanders new england journal lymphoma lung cancer asco childhood cancer aggarwal crs jude children research hospital native hawaiians bruton perelman school egfr kras md anderson clinical oncology cancer survivorship associate member myeloma texas md anderson cancer center myc neuroblastoma division head cd3 asco annual meeting elara cd20 michael wong conquer cancer research roundup abramson cancer center cln ibrutinib net podcasts swog bcl2 hispanic white r chop charu aggarwal hematology oncology division

New Evidence With BTK Inhibitor Therapy in CLL and MCL From the Pan Pacific Lymphoma Conference 2022

Play Episode Listen Later Aug 30, 2022 28:34

In this episode, Julie M. Vose, MD, MBA, and Matthew S. Davids, MD, MMSc, discuss their choices of recent important trials presented at the Pan Pacific Lymphoma Conference 2022 evaluating the use of BTK inhibitors in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The discussion includes analyses of: BRUIN (CLL/small lymphocytic lymphoma [SLL]): phase I/II study of pirtobrutinib for previously treated CLL (including previous BTK inhibitor)SEQUOIA: phase III study evaluating cohort 1 of zanubrutinib vs bendamustine/rituximab in untreated CLL/SLL without del(17p)MAJIC: phase III trial in progress of acalabrutinib + venetoclax vs venetoclax + obinutuzumab in previously untreated CLLBRUIN (MCL): phase I/II study of pirtobrutinib for previously treated MCL (including previous BTK inhibitor)BRUIN MCL-321: phase III trial in progress of pirtobrutinib vs investigator's choice acalabrutinib, ibrutinib, or zanubrutinib in previously treated, BTK inhibitor–naive MCLBRIDGE: series case report from phase II study evaluating zanubrutinib-based induction and maintenance in young patients with MCLPresenters: Julie M. Vose, MD, MBAChief, Division of Oncology and HematologyNeumann M. and Mildred E. Harris ProfessorDepartment of Internal MedicineUniversity of Nebraska Medical CenterOmaha, NebraskaMatthew S. Davids, MD, MMScAssociate Professor of MedicineHarvard Medical SchoolDirector of Clinical ResearchDivision of LymphomaDana-Farber Cancer InstituteBoston, MassachusettsLink to full program:https://bit.ly/3OQ6634

therapy conference mba md bridge oncology sequoia lymphoma btk bruin mcl new evidence inhibitor cll majic mantle cell lymphoma pan pacific sll ibrutinib matthew s davids

Data From SHINE Study Shows Significant Breakthrough for Patients with Mantle Cell Lymphoma

Rare Disease Discussions

Play Episode Listen Later Aug 12, 2022 3:30

Michael L. Wang, MD, Professor, Department of Lymphoma & Myeloma at the University of Texas MD Anderson Cancer Center, discusses results of the phase 3 SHINE study which evaluated the safety and efficacy of ibrutinib in combination with bendamustine and rituximab in patients 65 years of age or older with newly diagnosed mantle cell lymphoma. These data were recently presented at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting and were published in The New England Journal of Medicine.Mantle cell lymphoma is a rare form of non-Hodgkin's lymphoma in which B-cells become cancerous and form tumors in the lymph nodes that can quickly spread to other regions. It commonly affects people over the age of 65 who typically cannot tolerate intensive chemoimmunotherapy and stem cell transplantation, resulting in poor clinical outcomes.As Dr. Wang explains, the SHINE study enrolled 523 patients 65 years of age or older with newly diagnosed mantle cell lymphoma. All participants were randomly assigned to receive 560 mg ibrutinib QD or placebo in combination with bendamustine and rituximab for a maximum of six 28-day cycles. Participants with a complete response or partial response continued to receive maintenance therapy with rituximab every second cycle for a maximum of 12 additional doses. Ibrutinib or placebo was administered daily until progressive disease or unacceptable toxicity.

New Evidence With BTK Inhibitor Therapy in CLL and MCL From EHA 2022

Play Episode Listen Later Jul 21, 2022 26:22

In this episode, Othman Al-Sawaf, MD, and Lydia Scarfò, MD, discuss key trials presented at EHA 2022 evaluating the use of BTK inhibitors in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The discussion includes analyses of: GAIA/CLL13: phase III trial of time-limited venetoclax + obinutuzumab ± ibrutinib vs chemoimmunotherapy as first-line therapy for CLLFLAIR: randomized, adaptive-design phase III trial with data reported from ibrutinib + venetoclax and ibrutinib arm; includes measurable residual disease–defined therapy durationBRUIN: phase I/II study of pirtobrutinib for previously treated CLL (including previous BTK inhibitor)SHINE: phase III study of ibrutinib with bendamustine + rituximab and rituximab maintenance in older patients with MCLPresenters:Othman Al-Sawaf, MDFaculty of MedicineUniversity Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, GermanyVisiting ScientistThe Francis Crick InstituteUCL Cancer Institute, University College London London, United KingdomLydia Scarfò, MDLaboratory of B-Cell Neoplasia, Division of Experimental OncologyStrategic Research Program on CLLUniversità Vita Salute San Raffaele and IRCCS Ospedale San RaffaeleMilano, ItalyLink to full program:https://bit.ly/3OQ6634

therapy md shine gaia flair btk bruin mcl new evidence mrd inhibitor cll chronic lymphocytic leukemia mantle cell lymphoma eha sll ibrutinib

Long-term ibrutinib-rituximab vs FCR in CLL, procoagulant platelet sentinels in prevention of inflammatory bleeding, and new SERPINC1 variants in thrombophilia

medical prevention long term bleeding oncology variants medical research inflammatory sentinels hematology platelet rituximab fcr ibrutinib

Play Episode Listen Later Jul 14, 2022 18:30

In this week's episode we'll compare the long-term outcomes of ibrutinib-rituximab combination therapy versus FCR chemoimmunotherapy in chronic lymphocytic leukemia, discuss the role of procoagulant platelet sentinels in inflammatory bleeding, and learn more about variants in the SERPINC1 gene encoding antithrombin that cause severe thrombophilia.

New Evidence With BTK Inhibitor Therapy in CLL and MCL From ASCO 2022

Play Episode Listen Later Jul 6, 2022 32:16

In this episode, Brad S. Kahl, MD, and Anthony Mato, MD, MSCE, discuss their choices of 3 recent important trials presented at ASCO 2022 evaluating the use of BTK inhibitors in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The discussion will include analyses of: The SHINE trial evaluating the addition of ibrutinib to bendamustine/rituximab followed by rituximab maintenance in the first-line setting for older patients with MCL3-year follow-up analysis from the CAPTIVATE fixed-duration cohort of first-line ibrutinib plus venetoclax for CLL/small lymphocytic lymphomaPhase I/II study of zilovertamab, an anti-ROR1 antibody, plus ibrutinib in MCL or CLLPresenters:Brad S. Kahl, MDProfessor of MedicineDepartment of Medical OncologyWashington University School of MedicineSt Louis, Missouri Anthony Mato, MD, MSCEAssociate ProfessorDivision of LeukemiaMemorial Sloan Kettering Cancer CenterNew York, New YorkSee full program:https://bit.ly/3OQ6634

therapy md shine captivate btk asco mcl new evidence inhibitor cll mantle cell lymphoma rituximab ibrutinib mdprofessor

ASCO 2022: What's New in Mantle Cell Lymphoma

PCE

Play Episode Listen Later Jun 30, 2022 24:26

In this episode, Tycel J. Phillips, MD, and Amy Goodrich, RN, MSN, CRNP-AC, provide expert insights on key data presented at ASCO 2022 for mantle cell lymphoma regarding:Results from the phase III SHINE study of the addition of ibrutinib the first-line BR followed by rituximab maintenance in older patients with MCLUpdated results from the phase II ZUMA-2 study evaluating brexucabtagene autoleucel for patients with R/R MCLResults from a phase I/II study of the ROR1 humanized monoclonal antibody, zilovertamab, in combination with ibrutinib for patients with R/R MCL, MZL, or CLL/SLLPreliminary results from a phase I study of the humanized ROR1xCD3 bispecific antibody, NVG-111, in R/R CLL and MCL after ≥2 previous therapiesPresenters:Tycel J. Phillips, MD Maria Reinhardt Decesare Research Professor of Blood Cancers and Bone Marrow TransplantationAssociate Professor of MedicineUniversity of Michigan Rogel Cancer Center Ann Arbor, MichiganAmy Goodrich, RN, MSN, CRNP-ACResearch Associate, Department of MedicineJohns Hopkins UniversityNurse Practitioner, Department of MedicineThe Sidney Kimmel Comprehensive Cancer CenterBaltimore, MarylandContent supported by educational grants from Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Link to full program, including a downloadable highlights slideset:https://bit.ly/3yufCU4

md llc shine results phillips rn msn lymphoma asco mcl mantle cell lymphoma nvg ibrutinib janssen scientific affairs r r mcl abbvie company amy goodrich r r cll pharmacyclics llc

ASCO 2022: Advances in CLL/SLL

PCE

Play Episode Listen Later Jun 30, 2022 37:17

In this episode, John M. Burke, MD, a leading expert, and Amy Esposito, FNP-C provide expert insights on key data presented at the 2022 ASCO annual conference for CLL/SLL regarding:Updated response and safety results after 3 years of follow-up from the phase II CAPTIVATE study of ibrutinib and venetoclax in patients with previously untreated CLLUpdated response and remission rates after 4 years of follow-up from a phase II trial of obinutuzumab, ibrutinib, and venetoclax in patients with either treatment-naïve or relapsed/refractory CLLProgression free survival and safety results after 5 years of follow-up from the ELEVATE-TN phase III study of Acalabrutinib ± Obinutuzumab vs Obinutuzumab + Chlorambucil as first-line therapy in CLLAssessments of whether racial and/or ethnic identity, and socioeconomic status are prognostic factors of survival in CLLPresenterJohn M. Burke, MDRocky Mountain Cancer CentersAurora, ColoradoModerator Amy Esposito, FNP-CNurse PractitionerRocky Mountain Cancer CenterAurora, Colorado

colorado md advances asco cll fnp c chronic lymphocytic leukemia sll ibrutinib small lymphocytic lymphoma

4.62 - SHINE - Ibrutinib BR vs BR; Limitations to the trial

Plenary Session

Play Episode Listen Later Jun 4, 2022 18:01

Continuous vs. Fixed, 3 vs 2, PFS is the primary endpoint No OS Bad crossover Lots to discuss here I will be covering all the major ASCO papers on @PlenarySession Subscribe to my substack https://vinayprasadmdmph.substack.com/

health medicine trial policy shine limitations continuous oncology asco pfs ibrutinib

Fixed-duration ibrutinib + venetoclax for CLL, aryl hydrocarbon receptor in idiopathic pneumonia syndrome, and VWF propeptide and multimerization

Play Episode Listen Later Jun 2, 2022 22:25

In this week's episode, we discuss results from the international phase 2 CAPTIVATE study showing that in patients with treatment-naive CLL, fixed-dose ibrutinib plus venetoclax yields deep and durable responses and promising progression-free survival. We'll also explore data that show that aryl hydrocarbon receptor is a critical inflammation checkpoint in the lung epithelium—a finding that may have therapeutic implications for idiopathic pneumonia syndrome. Lastly, we'll review new insights into the role of von Willebrand Factor propeptide in facilitating multimer formation, shedding light on a potential novel treatment approach for type 2a von Willebrand disease.

medical syndrome oncology pneumonia medical research captivate receptor hematology idiopathic cll hydrocarbons willebrand ibrutinib aryl

ASCO22: Key Advances in Hematologic Malignancies

ASCO Daily News

Play Episode Listen Later May 27, 2022 17:49

Dr. John Sweetenham, of the UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and Dr. Marc Braunstein, of NYU Langone Health, discuss key data from the CAPTIVATE and GRIFFIN trials and other compelling studies in hematologic malignancies featured at the 2022 ASCO Annual Meeting. Dr. John Sweetenham: Hello. I'm John Sweetenham, the associate director for Clinical Affairs at UT Southwestern Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News podcast. For my guest today, I'm pleased to introduce Dr. Marc Braunstein, a hematologist, and oncologist at NYU Perlmutter Cancer Center. We'll be discussing key posters on advances in hematologic malignancies that will be featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts. Marc, it's great to have you on the podcast today. Dr. Marc Braunstein: Thank you, John. It's a pleasure to be here. Dr. John Sweetenham: So, Marc, there are going to be some very interesting abstracts with some provocative results presented at the ASCO Annual Meeting this year. I know we've selected a number of these to speak about today, beginning with Abstract 8027 on the subject of multiple myeloma. And this I think is a long-term follow-up study for long-term survivors of multiple myeloma more than 12 years out now. Can you comment on this and let us know what you believe the key takehomes from this study are? Dr. Marc Braunstein: Sure. Absolutely, John. So, this was a prospective registry that has been in place since 2009, and it's composed of various practice settings, but primarily community practices where most patients get their myeloma care. And what they did was they looked at about 1,400 patients with newly diagnosed multiple myeloma across 250 sites in the U.S. between 2009 and 2011 who were included in the registry. The participants also filled out the quality-of-life surveys, and they compared a group of long-term survivors who had more than 8 years of follow-up to patients who were not long-term survivors below that 8-year threshold. So, about 20% were in the long-term survival group and 80% in the non-long term survival group. And they basically characterized those 2 groups. What they found was that the individuals who did have long-term survival were generally younger—median age of 62 versus 68, and had better performance status, were more likely to receive stem cell transplants, about 66 versus 60%. And therefore, the implication of this is that patients who fit those criteria may have a better prognosis in addition to the other cytogenetics and other factors we use as prognostic indicators. And what was also interesting was that the 8-year overall survival of the overall group was about 36%. So, we still have room to go in terms of bringing new therapies to extend survival in this condition. And only 20% of the total population were long-term survivors at that 8-year threshold. So, those were the general findings of the abstract. Dr. John Sweetenham: Do you think it gives us new information on patient selection for more intensive therapies upfront? Dr. Marc Braunstein: Well, I think it certainly tells us which patients are more likely to have longer-term survival. I think we know in multiple myeloma that it's essential to really use the patient's presenting features, their disease features, their comorbidities, and their degree of fitness or frailty to guide how intensive a therapy or regimen we can devise for that individual patient. But I think it certainly says that if you have a patient who is on the younger side of the spectrum, who is eligible for stem cell transplant, who has a better performance status, those are the patients that are more likely to have the long-term survival. It doesn't necessarily say that if you're not in that category, you won't have long-term survival, but on average, those were the patients who fared better in the long term. Dr. John Sweetenham: Okay. So, staying for a little while on the subject of multiple myeloma, Abstract 8037 is really addressing a very different question. It's the application of circulating tumor DNA analysis and its association with relapse in patients with refractory myeloma. Would you comment a little on this and maybe let us know what you think the significance of this will be for the future? Dr. Marc Braunstein: Sure. My colleagues in the solid tumor space are using circulating tumor DNA regularly and in the myeloma field, we're a little bit jealous of them. So, it's helpful to have a study like this that's looking at circulating peripheral blood markers, in this case circulating tumor DNA, to help guide various prognostic or predictive indices that will help us guide therapeutic decisions. So, this was a study where they looked at patients who were enrolled in a phase 2 study of a free-drug regimen of carfilzomib-thalidomide-dexamethasone the MM17 study, and they took 50 transplant eligible multiple myeloma patients who were refractory to their first line of therapy, and they collected bone marrow samples and peripheral blood at 3 time points at the third cycle of treatment and at the end of the study or at the point of refractoriness to that regimen. They collected about 187 samples in total. They used a sequencing technique to determine the variance of 22 gene signatures known to be mutated in multiple myeloma. And what they found was a particular gene signature that was associated with shorter progression-free and overall survival in that phase 2 study. And those genes included known oncogenic drivers, including BRAF genes, ATM, and P53. What was particularly interesting among the circulating tumor DNA mutations was that they were found in about 88% of patients at the start of the study. So, what that tells us is, number 1, circulating tumor DNA offers a wealth of information that can be highly valuable in multiple myeloma, which is a disease where we typically rely on the bone marrow to assess the status of the plasma cells and status of the mutation profile. And number 2, that many of these mutations may be present earlier on in a disease that we know evolves in a clonal way that leads to disease progression. So, I think there's still a lot of information we have to learn about the utility of circulating tumor DNA in myeloma, but this study certainly shows that there's a lot to be explored in terms of the mutational profile and peripheral blood in myeloma. Dr. John Sweetenham: A couple of questions that arise for me out of this study. First of all, do you think this is going to have any implications for future study design and patient selection? Dr. Marc Braunstein: Definitely. I think the whole field in multiple myeloma is progressing quickly in terms of how we assess response, how we use minimal residual disease, and moving more towards using novel markers in peripheral blood, including mass spectrometry, and now perhaps circulating tumor DNA to look at surrogate markers for survival. And so, what this abstract is showing is that we could potentially use circulating tumor DNA both as prognostic markers, potentially as disease response markers, and prognostic markers to guide which patients may be more likely to have shorter survival. So, I think this has a lot of implications for how we design future studies. Dr. John Sweetenham: Yeah. And the second question, do you think this is the beginning of the end of bone marrow analysis in multiple myeloma? Dr. Marc Braunstein: So, I can tell you if it is, patients I think will be very happy and so will clinicians because we really want to know at the core what the degree of residual disease is in a patient. And right now, the only way to do that is through a bone marrow biopsy. And so, I think that this is the beginning of the use of peripheral blood studies with higher resolution to allow us to gain more information on patients that hopefully will allow us to obviate the need for more invasive testing like bone marrow biopsies. Dr. John Sweetenham: Yeah, absolutely. Thanks. Just changing gears now, moving on to Abstract 7050. This is an abstract that addresses what I think we'd all agree is becoming an increasingly important question in the management of chronic myeloid leukemia (CML), and that is number 1, is it safe to discontinue therapy in responding patients? And number 2, when is it safe to discontinue that therapy? Dr. Marc Braunstein: So, this is an abstract that is looking primarily at CML. You know that we're making a lot of progress when we can begin to talk about discontinuation and de-escalation of therapy. And so, in the field of CML, the use of tyrosine kinase inhibitors (TKIs) and the targeting of the BCR-ABL mutation has brought about tremendous progress in patients in the chronic phase. So, there have been several retrospective studies that have looked at the role of discontinuing one of the TKIs. Most of the studies have focused on imatinib since that was the first one that was discovered, but they've looked at others in the class as well. What struck me the most is that there's a remarkable consistency between these studies. So, when you discontinue one of these TKIs, the percentage of patients who remain in remission is somewhere between 40 to 50%. And what this abstract looked at was a single institution retrospective assessment of 284 patients with CML, between 1999 and 2017, who were treated with a TKI for their CML and then subsequently discontinued the therapy. Now, what's worth noting in the various studies that have looked at discontinuation therapy is that patients who were taken off of the TKI generally were in a good molecular remission, MR 4 or 4.5, for at least 2 or 3 years. And in this study, about 70% of patients had electively discontinued and 24% of patients stopped due to adverse events. So, it wasn't necessarily guided by their response to treatment at the time of discontinuation. What they found actually was fairly consistent with the literature that at a median follow-up of 36 months after TKI discontinuation, about 19% lost their molecular remission and 88% had achieved a molecular remission after resuming therapy. And that is consistent with the literature that fortunately, even if a patient loses their molecular remission off of the TKI therapy, the majority of patients will go back into molecular remission when you re-challenge them. Dr. John Sweetenham: Important data, indeed. And you know, on something of a similar theme, the next abstract that we're going to look at is the Abstract 7519. In this case, in chronic lymphocytic leukemia (CLL), and certainly, those of us who remember when ibrutinib was initially introduced into the second-line treatment of CLL, didn't really know whether discontinuation or fixed duration treatment with agents like this was going to be something that we could pursue or whether treatment with these drugs was going to be indefinite. This abstract certainly addresses that specific question, and again, I'm interested in your insights into this. Dr. Marc Braunstein: Sure. So, this is an abstract looking at CLL, where we've really begun to move away from chemotherapy, and we have a variety of targeted oral therapies that target the underlying pathology of this leukemia. And so, as you mentioned, ibrutinib is approved both in the relapsed and more recently in the frontline setting, wherein the RESONATE-2 study that was published in the New England Journal of Medicine in 2015, there was actually an overall survival benefit of ibrutinib even in higher-risk patients. So, the CAPTIVATE study is an ongoing phase 2 study that is looking at whether we can improve the efficacy of single-agent ibrutinib in the first-line setting when combined with venetoclax. Ibrutinib targets protein tyrosine kinase and venetoclax targets Bcl-2, and that combination is hypothesized to further weaken the resistance of CLL and lead to better outcomes. So, this was a multicenter phase 2 study. And in this abstract, they looked at the 3-year follow-up of patients who were actually able to discontinue therapy on this regimen. So, just as a bit of background, ibrutinib is typically continued until progression, and venetoclax as it's been studied in the first-line setting with obinutuzumab is given for about 12 months. So, in this study, at 3-year follow-up, they looked at the patients in the cohort who were off therapy and looked at the percentage of patients who maintained a complete remission at 3 years. And that complete remission rate was about 57%. The majority of patients, greater than 95% of patients, were alive at 3 years even in the high-risk cohort. So, I think the implications of the study is that upfront or oral targeted therapies when you combine ibrutinib and venetoclax really produce tremendous responses that are durable, and it's found even in the high-risk patients who are expected not to do quite as well at 3 years. Dr. John Sweetenham: Yeah, I agree. I think it's very reassuring actually to see these durable responses with this fixed duration regimen. And to conclude, Abstract 8011 was an abstract which addressed treatment in the first-line setting for multiple myeloma. And again, I wonder if you could comment on this study. Dr. Marc Braunstein: Sure! So, this is a study looking at the GRIFFIN regimen, which was a phase 2 randomized study of daratumumab (DARA), plus lenalidomide, bortezomib, and dexamethasone. So, DARA RVd versus RVd alone. In that study, the primary endpoint was stringent, complete remission, and it has been previously presented and published that the stringent complete remission (CR) rate was significantly improved, 42% versus 32%, when you include daratumumab upfront. In this abstract, they looked at the sustained rate of minimal residual disease negativity, which is basically the deepest possible remission you can achieve in upfront therapy and in myeloma. What they found was that, again, when you looked at the quadruplet regimen versus the triplet regimen, the rates of minimum residual disease (MRD) negativity were just improved with the quad regimen. So, at a median follow-up of 38.6 months, there were about 54 versus 20% of patients who were MRD negative at 12 months amongst the patients who had achieved a CR, and 59 versus 17% MRD negative among the patients who achieved a stringent CR favoring the daratumumab arm. So, I think this abstract shows the benefit of including a monoclonal antibody upfront in newly diagnosed patients with myeloma combined with stem cell transplant and maintenance, allowing for sustained MRD negativity. Dr. John Sweetenham: Do you think this represents a new standard of care? Dr. Marc Braunstein: I do. At our institution, we've adopted this regimen for most newly diagnosed transplant-eligible patients. I think the data clearly show an improved depth of response and MRD negativity rates, and I think that there are a number of ongoing studies looking at the role of monoclonal antibodies in the maintenance phase as well. I'm especially excited this year, at ASCO Annual Meeting there's a plenary session involving myeloma looking at patients who received RVd upfront and then went for transplant. But I think we can improve on that regimen by including monoclonal antibodies and immunotherapies upfront, and I do think it represents a new era of immunotherapies in multiple myeloma. Dr. John Sweetenham: Well, thanks, Marc. I mean, to your last point, it sounds as if there is a lot, including these abstracts, to look forward to at the upcoming ASCO meeting. So, we really appreciate you sharing your insights into these abstracts with us today. Dr. Marc Braunstein: Sure. My pleasure. Thank you for having me, John. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstract discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Marc Braunstein: Consulting or Advisory Role: Celgene, Janssen, AstraZeneca, Amgen, Takeda, Verastem, Celgene, Janssen, Karyopharm Therapeutics, Epizyme, Morphosys, Takeda, Pfizer Research Funding (Inst): Janssen, Celgene/BMS Travel, Accommodations, Expenses: Takeda 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.

Expert Answers to Key Questions on Current and Emerging BTK Inhibitor Therapies for CLL and MCL

Play Episode Listen Later Mar 31, 2022 28:05

In this episode, Jeff P. Sharman, MD; Matthew S. Davids, MD, MMSc; and Anthony Mato, MD, MSCE, answer questions from a live CCO webinar on current best practices and emerging strategies in BTK inhibitor therapy for patients with chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), with questions including:For patients with CLL, when should acalabrutinib-, ibrutinib-, or venetoclax-based regimens be considered?What is the optimal therapy for a patient with del(17p) CLL?When should an anti-CD20 antibody be added to BTK inhibitor therapy for patients with CLL?What are best practices in the use of BTK inhibitors for patients with MCL?How can BTK inhibitor resistance occur?How might investigational noncovalent BTK inhibitors be used should they be approved?What are key adverse events with BTK inhibitors?Presenters:Jeff P. Sharman, MD (chair)Medical DirectorHematology ResearchUS Oncology Willamette Valley Cancer InstituteEugene, Oregon Matthew S. Davids, MD, MMScAssociate Professor of MedicineHarvard Medical SchoolDirector of Clinical ResearchDivision of LymphomaDana-Farber Cancer InstituteBoston, MassachusettsAnthony Mato, MD, MSCEAssociate ProfessorDivision of LeukemiaMemorial Sloan Kettering Cancer CenterNew York, New YorkContent based on an online CME program supported by an educational grant from Lilly. For further information concerning Lilly grant funding, visit https://bit.ly/3wXOsV5. Link to full program:https://bit.ly/3NEpsYQ

current md resistance emerging therapies cco cme key questions btk bruin mcl inhibitor cll chronic lymphocytic leukemia mantle cell lymphoma cd20 ibrutinib matthew s davids

Advances in B-Cell Lymphomas: Understanding Current Treatment Approaches

Play Episode Listen Later Feb 25, 2022 30:57

In this episode, Julie M. Vose, MD, MBA; Brad S. Kahl, MD; and John P. Leonard, MD, discuss treatment approaches for patients with B-cell lymphomas, including information on: Follicular lymphomaMarginal zone lymphomaMantle cell lymphomaDiffuse large B-cell lymphomaPosttransplant lymphoproliferative disorderPresenters:Julie M. Vose, MD, MBAChief, Division of Oncology and HematologyNeumann M. and Mildred E. Harris ProfessorDepartment of Internal MedicineUniversity of Nebraska Medical CenterOmaha, NebraskaBrad S. Kahl, MDProfessor of MedicineDepartment of Medical OncologyWashington University School of MedicineSt Louis, MissouriJohn P. Leonard, MDRichard T. Silver Distinguished Professor of Hematology and Medical OncologyProfessor of MedicineWeill Cornell MedicineNew York Presbyterian HospitalNew York, New YorkLink to the complete program, including downloadable slidesets, expert commentaries, an on-demand webcast, and treatment resource guides:https://bit.ly/3tb47wU

current mba md treatments approaches advances oncology lymphoma mcl augment hematology gallium follicular lymphoma mantle cell lymphoma rituximab marginal zone lymphoma ibrutinib diffuse large b-cell lymphoma blinatumomab mdprofessor john p leonard idelalisib

Expert Insights on Advances in Immune Thrombocytopenia