Podcasts about ighv

Featuring an interview with Dr Catherine C Coombs, including the following topics: Case: A woman in her early 80s with dementia and newly diagnosed IGHV-mutated del(13q) chronic lymphocytic leukemia (CLL) receives initial treatment with zanubrutinib (0:00) Current and investigational initial therapy approaches for CLL (13:41) Case: A man in his late 40s under observation for asymptomatic CLL develops worsening symptoms and initiates treatment with venetoclax/obinutuzumab (28:15) Phase III AMPLIFY trial of fixed-duration acalabrutinib combined with venetoclax with or without obinutuzumab as first-line treatment for CLL (36:02) Other novel venetoclax combinations for the treatment of CLL (43:36) Case: A man in his mid 70s with multiregimen-refractory CLL receives pirtobrutinib (46:51) Personal perspectives on the activity and tolerability of pirtobrutinib; sequencing pirtobrutinib and chimeric antigen receptor T-cell therapy for patients with CLL (51:16) CME information and select publications

Featuring perspectives from Dr Jennifer Woyach, including the following topics: AMPLIFY — First-Line Trials Combining Bruton Tyrosine Kinase (BTK) Inhibitors with Venetoclax Introduction (0:00) Case: An African American man in his mid 40s with progressive lymphadenopathy in the neck is diagnosed with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with trisomy 12 and an SF3B1 mutation — Erik Rupard, MD (1:50) Pirtobrutinib Questions for the Faculty: Effectiveness and tolerability of pirtobrutinib for patients with CLL and disease progression on prior BTK inhibition — Zanetta S Lamar, MD (21:18) Choice of First-Line BTK Inhibitor Case: A woman in her mid 80s diagnosed with CLL more than 30 years ago now has relapsed/refractory, ibrutinib-intolerant disease — Warren S Brenner, MD (31:29) Cardiotoxicity of BTK Inhibitors  Case: A man in his early 70s with chronic atrial fibrillation requiring long-term anticoagulation is diagnosed with IGHV-unmutated CLL with del(13q), del(17p) and an XPO1 mutation — Bhavana (Tina) Bhatnagar, DO (34:53) Case: A man in his mid 70s with trisomy 12, IGHV-unmutated CLL has a history of congestive heart failure (ejection fraction 20% to 25%) resulting in multiple hospital admissions — Laurie Matt-Amaral, MD, MPH (37:51) CLL and COVID-19 Vaccinations; Role of MRD Testing; Anti-CD20 Antibodies Case: A man in his early 60s with CLL receives first-line obinutuzumab/venetoclax and has a moderate infusion reaction to obinutuzumab — Dr Rupard (41:17) Case: A man in his early 60s with CLL and well controlled autoimmune hemolytic anemia on ibrutinib is switched to zanubrutinib — Dr Lamar (45:26) Questions for the Faculty: CLL and COVID-19 vaccinations; role of MRD testing; anti-CD20 antibodies — Dr Brenner (49:23) Case: An Amish man in his mid 60s requires treatment for CLL but is paying for treatment “out of pocket” — Dr Rupard (55:33) CME information and select publications  

Featuring perspectives from Dr Nicole Lamanna, including the following topics: Introduction (0:00) Case: A man in his late 60s with IGHV-mutated chronic lymphocytic leukemia (CLL) (trisomy 12) and progressive adenopathy — Bhavana (Tina) Bhatnagar, DO (1:22) Case: A woman in her mid 70s with IGHV-unmutated, del(13q) CLL and fatigue — Erik Rupard, MD (19:57) Case: A woman in her mid 80s with del(13q) CLL under watchful waiting develops progressive symptoms — Shams Bufalino, MD (30:00) Case: A woman in her early 60s diagnosed with small lymphocytic leukemia (SLL) now with disease progression on ibrutinib — Warren S Brenner, MD (33:08) Current role of pirtobrutinib; CAR T-cell therapy; Richter's transformation — Dr Brenner (36:04) Case: A man in his mid 40s with SLL who received second-line venetoclax/rituximab — Yanjun Ma, MD (50:01) CME information and select publications

Featuring perspectives from Dr Matthew S Davids, including the following topics: Introduction: Is Chronic Lymphocytic Leukemia (CLL) the New Chronic Myeloid Leukemia? Cases We Didn't Hear About Last Week (0:00) Case: A man in his early 70s with IGHV-unmutated CLL (trisomy 12, del[17p]) receives ibrutinib for several years and is switched to acalabrutinib to lower the risk of cardiotoxicity — Warren S Brenner, MD (16:39) Case: A man in his mid 70s with relapsed atypical del(17p) CLL who previously received ibrutinib receives venetoclax/obinutuzumab — Bhavana (Tina) Bhatnagar, DO (22:10) Case: A woman in her early 80s with IGHV-mutated CLL begins treatment with zanubrutinib and 6 months later develops altered mental status due to cryptococcal meningitis — Erik Rupard, MD (33:00) Case: A woman in her early 80s with relapsed CLL (del[17p]/TP53 mutation) develops Stevens-Johnson syndrome while receiving ibrutinib — Spencer H Bachow, MD (38:21) Case: A man in his mid 90s with del(13q) CLL under observation for 12 years begins treatment with zanubrutinib and develops significant bruising/ecchymosis — Dr Rupard (41:14) Case: A woman in her late 70s with relapsed del(13q) CLL receives acalabrutinib and develops hyperleukocytosis — Dr Bhatnagar (45:44) Case: A woman in her mid 80s with rising white blood cell counts and asymptomatic recurrence of CLL (trisomy 12) receives rituximab with subsequent addition of venetoclax — Dr Brenner (50:20) Transformed CLL; CAR T-Cell Therapy (53:38) Journal Club with Dr Davids (54:26) CME information and select publications

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

Featuring perspectives from Dr Bita Fakhri, including the following topics: Overview of select presentations from ASH 2023; recent FDA approval of lisocabtagene maraleucel (0:00) 6-year follow-up from the Phase III CLL14 trial of first-line venetoclax/obinutuzumab versus chlorambucil/obinutuzumab for chronic lymphocytic leukemia (CLL) (7:36) Updates from ASH 2023 from the Phase III FLAIR study of minimal residual disease (MRD)-guided ibrutinib in combination with venetoclax for previously untreated CLL (13:28) 57-month follow-up from the Phase III GLOW trial of fixed-duration ibrutinib/venetoclax for previously untreated CLL (22:28) Current clinical role of MRD testing for CLL (28:11) Key findings from 5-year follow-up of the Phase II CAPTIVATE study for patents with CLL/small lymphocytic leukemia (SLL) with relapse after first-line fixed-duration ibrutinib/venetoclax (36:43) 6-year update from the Phase III ELEVATE-TN trial of acalabrutinib with or without obinutuzumab for treatment-naïve CLL (41:57) Updates from ASH 2023 for the management of relapsed/refractory CLL (54:30) Recent updates for the management of double-refractory CLL (58:05) Novel therapies under investigation for patients with CLL/SLL (1:10:57) Key findings guiding the clinical management of Richter's transformation (1:13:44) Case: A man in his early 80s with IGHV-unmutated del(17p) CLL experiences disease progression 3 years after completing second-line venetoclax-based therapy (1:22:17) CME information and select publications

On this week's episode we'll discuss the findings from a long-term follow up study of fludarabine, cyclophosphamide, and rituximab in IGHV-mutated CLL, learn more about the impact of genetic alterations and minimal residual disease in adults with KMT2A-rearranged B-cell precursor ALL, and discuss a pre-clinical study of reinforced immunotherapy for myeloma using a new bispecific antibody-based approach.

Dr. John Sweetenham and Dr. Marc Braunstein discuss the role of maintenance therapy in high-risk multiple myeloma, advances in myelodysplastic syndromes in the COMMANDS study, the promise of bispecific antibodies in the pivotal EPCORE NHL-1 in relapsed/refractory large B-cell lymphoma, and improving outcomes for patients with chronic lymphocytic leukemia in the CAPTIVATE trial.  TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the associate director for cancer network clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News Podcast. My guest today is Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center. Today, we'll be discussing key posters and oral abstracts highlighting advances in hematologic malignancies that will be featured at the 2023 ASCO Annual Meeting.   You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod.  Dr. John Sweetenham: So, Marc, thanks for returning to us and coming to join us on the podcast today. Dr. Marc Braunstein: Thanks for inviting me back. Dr. John Sweetenham: I'd like to start out with Abstract 8001. This is a study which is addressing the role of maintenance therapy in patients with high-risk multiple myeloma. Could you take us through this study and the key take-home points that you think are the most important ones? Dr. Marc Braunstein: Sure, absolutely. So, the first abstract that we're going to discuss is an oral abstract being presented by Dr. Nooka regarding maintenance therapy in high-risk multiple myeloma patients. Outcomes of patients with multiple myeloma are clearly improving, yet those with high-risk cytogenetic abnormalities, which represent about 10-20% of all multiple myeloma, tend to have poorer survival, and worst among these are those with what's called ultra-high-risk or double-hit multiple myeloma who have more than 1 high-risk cytogenetic abnormality. So, this study looked at maintenance therapy following stem cell transplantation in 26 high-risk patients, about 59% of whom had double hit disease, representing very high-risk disease. This was a phase II study looking at using carfilzomib, pomalidomide, and dexamethasone in high-risk multiple myeloma patients who achieved at least a partial remission following stem cell transplant. There were 26 patients enrolled. The median age was 60. Of note, about 59% of patients were Black, which is important because these patients tend to be historically underrepresented in studies. And what they found was that at study entry, about 24% of patients were in a complete remission or better, and that deepened to 79% while on the study. And the median time to best response was 2 months, which is fairly brisk. With a median follow-up of about 26 months, the 36-month progression-free survival was 63%, and the overall survival was 72%, which is impressive, again in the context of patients who have very high-risk disease. So, although it remains to be determined what the optimal regimen or duration of maintenance should be in multiple myeloma, clearly, combination therapy is effective and should be used in patients who have high-risk or ultra-high-risk multiple myeloma. Dr. John Sweetenham: Great. Thanks, Marc. So, as you say, I mean, clearly the take-home message is around the effectiveness of this type of maintenance therapy. I just have a couple of quick follow-up questions for you. The first of those is, where do you see this going next? I mean, in your opinion, what would be the next logical study with this combination or similar combinations? And then secondly, what do you see on the horizon for those patients with very high-risk myeloma, particularly the double-hit population that you just mentioned? Dr. Marc Braunstein: It's a paradigm in multiple myeloma that combination therapy tends to be more effective as long as we're able to manage the adverse events that come with additional combinations. And we've been able to succeed in that regard with quadruplet regimens, even now that we have monoclonal antibodies that tend to be better tolerated and more targeted in nature. In terms of maintenance therapy, single-agent lenalidomide has been the long-standing agent of use for the majority of patients. But we now understand that the combination of an immunomodulator like lenalidomide and a proteasome inhibitor like bortezomib or carfilzomib is more effective for patients with higher risk disease.   We also have data from various upfront studies of quadruplet regimens, such as the FORTE study, which looked at carfilzomib and lenalidomide maintenance after transplant that shows that we can improve progression-free survival in all comers with multiple myeloma following transplants. So, I think down the road we're going to be looking at more use of combination therapies and maintenance. And as far as for high-risk patients, whether that's going to be using monoclonal antibodies in maintenance or combination proteasome inhibitors and immunomodulators or even other immunotherapies like bispecific antibodies as maintenance in the future remains to be determined, but clearly, for high-risk patients, we should be using combination therapies. Dr. John Sweetenham: Thanks, Marc. Let's change gears a little now and take a look at Abstract 7003, which addresses patients with myelodysplastic syndrome. This study addresses the efficacy and safety results from a study of luspatercept versus epoetin alfa in low-risk myelodysplastic syndrome. I wonder if you could describe this study and the results to us and maybe also for the benefit of our listeners, just mention quickly the mechanism of action of the experimental agent here.  Dr. Marc Braunstein: This is an oral abstract being presented by Dr. Garcia-Manero looking at a phase 3 study, as you mentioned, called the COMMANDS study, and this is looking at an agent called luspatercept in patients with low-risk myelodysplastic syndrome (MDS). So, patients with MDS can have inferior quality of life and survival when they become transfusion dependent. An earlier study called the MEDALIST study, which was published in the New England Journal of Medicine in 2020, randomized low-risk or intermediate-risk patients with MDS who were refractory or unlikely to respond to erythropoietin stimulating agents to either luspatercept, which is an agent that binds to TGF-beta family members and helps stimulate erythropoiesis. Patients were randomized in the MEDALIST study to luspatercept or placebo. And that study showed that luspatercept could improve a degree of anemia and lead to transfusion independence in certain patients. So, the COMMANDS study is a randomized controlled study that randomized 354 patients with low-risk MDS who were transfusion dependent and naive to an erythropoietin stimulating agent to receive either luspatercept or the erythropoietin stimulating agent erythropoietin alfa with the primary endpoint of transfusion independence at some time between 12 to 24 weeks. So, patients were randomized 1:1 to receive either luspatercept or epoetin alfa, and the primary endpoint again was transfusion independence. So, 354 patients were randomized in the study and the median treatment durations were 42 weeks of luspatercept and 27 weeks of epoetin alfa. And transfusion independence occurred in greater quantity in the patients who got luspatercept. For example, in the patients who received luspatercept at 8 weeks, transfusion independence was achieved in 74 versus 51% in the epoetin alfa group. So, in terms of treatment-related adverse events, they were fairly similar between the groups and consistent with the classes -  they were reported in 30% in the luspatercept group and 17% in the erythropoietin group, with no difference in patients who progressed to acute myeloid leukemia.  So, I think when it comes to MDS in low-risk patients, it's really important to preserve their quality of life by limiting their transfusion burden. And I think this study demonstrates that luspatercept continues to be an important part of the management in these low-risk patients. And whether or not you would start a patient with low-risk transfusion-dependent MDS on an erythropoietin stimulating agent or luspatercept is really addressed by this study showing that you can achieve greater rates of improvement in anemia and transfusion independence with luspatercept.  Dr. John Sweetenham: Great. Thanks, Marc. A really interesting study. And I do have one question for you about this study, which I think will make it clear to you that I am an expert neither in myelodysplastic syndrome nor in erythropoiesis. But my question is based on the mechanism of action. Is there any rationale for combining these 2 agents in future studies?  Dr. Marc Braunstein: Yes, it would potentially make sense to use 2 synergistic mechanisms to improve erythropoiesis. We would have to see what the potential for adverse events are. I think epoetin alfa tends to be a fairly low burden in terms of its side effect profile. Luspatercept can have some potentially dose-limiting side effects, such as GI side effects, but you can make dose adjustments to both of these medications. So we may need to find the correct doses of either of them in combination. But from a theoretical standpoint, it makes sense that these could potentially be synergistic, especially in patients who are likely to respond to erythropoietin by having a baseline lower erythropoietin level. Dr. John Sweetenham: Okay, let's move on in another change of gear now. And for the rest of the podcast, we're going to be talking about some studies in lymphoid malignancy, beginning with Abstract 7535, which is a follow-up of the phase 2 CAPTIVATE study which now has significantly extended follow-up from the original report. So Marc, can you walk us through this study and the outcomes to date? Dr. Marc Braunstein: Absolutely. So this is a poster being presented by Dr. Barr and it is looking at CLL, which is a field that is really moving away from chemotherapy for newly diagnosed patients, thanks to the development of novel targeted agents. The CLL14 trial, which was published in the New England Journal of Medicine in 2019, showed that fixed-duration venetoclax plus obinutuzumab improved progression-free survival and rates of negativity of minimal residual disease, or MRD, when compared to chlorambucil and obinutuzumab. So building on the success of that study, combining a monoclonal antibody and a BCL2 inhibitor, the CAPTIVATE study is a phase II study, which examines venetoclax with ibrutinib, the BTK inhibitor, and previously untreated CLL. So it's kind of combining 2of the novel targeted therapies in a fixed duration, similar to what was done in the CLL14 study where patients received 1 year of therapy and then stopped treatment.   So in the CAPTIVATE study, 154 patients were enrolled. This was a phase 2 study that included about 56% of higher-risk patients who had unmutated IGHV, and the median time on the study was 50 months, with a CR rate of 58% at a 4-year follow-up and an overall response rate of 96%, which is quite high, especially considering that more than half of patients had high-risk disease. The progression-free survival was 79% and the overall survival rate was 98% at 4 years. And when they looked at patients who had undetectable minimal residual disease, the 4-year overall survival rate was 100%, which also suggests that MRD can help serve as a predictive marker of longer-term survival. So I think we have to also consider what the side effects are of combining these 2 agents and the most common adverse events were hematologic, which is expected based on what we know about the 2 classes. So I think the implication of the study is that giving 2 oral agents for a fixed period of treatment for 12 cycles is a rational approach that may spare patients indefinite therapy and can lead to positive outcomes, including in patients who have high-risk features with CLL.  Dr. John Sweetenham: Yeah, the other interesting observation that was made in the abstract, which I found to be really encouraging, was the fact that a number of these patients apparently have been re-treated successfully upon progression with ibrutinib again, which seems to be somewhat reassuring as well.  Dr. Marc Braunstein: That's right. There were 4 patients who started re-treatment in the study and perhaps we'll see the outcomes of that small subgroup are at the poster presentation. But I think when we discuss fixed-duration treatment, it also opens the door to potentially re-challenging patients when they relapse. We know that when we stop single-agent BTK inhibitors, which are historically given indefinitely in patients with CLL, those patients who stop, many will relapse, but you can potentially re-challenge them with the BTK inhibitor. So this study with the CAPTIVATE trial gives us some liberty to discontinue therapy, but also considering re-challenging upon relapse.   Dr. John Sweetenham: Yeah, absolutely. Moving on to aggressive B-cell lymphoma, now, the next abstract I'd like to discuss with you is Abstract 7525. I find this one particularly interesting as the continued excitement around CAR T cell therapy for relapsed aggressive lymphoma remains high at the moment. It's intriguing that t cell-engaging antibodies also have been reported, at least, to have remarkable activity in this set of diseases. So can you take us through Abstract 7525 and what they're reporting?  Dr. Marc Braunstein: Absolutely. Bispecific antibodies represent an emerging field in multiple hematologic malignancies, and this is a class of antibodies that bind to both the tumor cell as well as T-cells, and activate T-cell immunity against the tumor cell. So epcoritamab is a bispecific antibody that binds to CD3, which is expressed on T cells, and CD20, which is expressed on B cells. And Thieblemont et al published results in the Journal of Clinical Oncology last year in a phase I/2 study that looked at epcoritamab in patients with diffuse large B cell lymphoma following 2 prior lines of therapy, and this was given subcutaneously until progression of disease. In that study, at a median follow-up of about 11 months, the overall response rate was 63% with 39% complete remissions.   So the EPCORE NHL-1 study, which is being presented at this year's ASCO meeting, is presenting the updated results of that study looking at patients with diffuse large B cell lymphoma that includes a small population as well of patients with high-grade B cell lymphomas and primary mediastinal B cell lymphomas who had at least 2 prior lines of therapy. In this presentation, 157 patients were included in this study, and 61% had primary refractory disease, and actually, 39% had prior CAR T-cell therapy, of whom 75% progressed within 6 months. So these were patients who were not only refractory to treatment but also had prior T-cell therapy.   So at a median follow-up of 20 months, the overall response rate was 63% and the complete response rate was again about 39%, and the median duration of complete remission was 21 months. In terms of overall survival, the median was about 19 months, which is substantial for this group of patients who really wouldn't be expected to respond very well to conventional therapies.   As we know, T-cell-engaging therapies, such as these bispecific antibodies or CAR T-cells have the potential risk for certain immune-related adverse events, including cytokine release syndrome or icons, and a neurologic syndrome related to the therapy. And it's worth noting that the CRS in this study was predominantly low-grade. There were only 3% of patients who had grade III CRS, and 9 patients, or 6% had grade I to II icons. I think that also reflects how we're better managing those side effects and intervening earlier. So I think the results are impressive from the standpoint of the population studied, who were quite refractory to treatment and show relatively high rates of response. In fact, the median overall survival was not reached in the overall population.   So I think what we take away from this abstract is that bispecific antibodies are going to play a vital role in the relapse-refractory setting for large cell lymphoma and may also offer an alternative to patients who aren't necessarily fit for CAR T-cell therapy, which plays a vital role in patients who are both refractory to first-line therapy or relapse-refractory to subsequent disease. So these are very encouraging results, and I'm sure we'll see randomized data as well in the future, further supporting the use of bispecific antibodies like epcoritamab.  Dr. John Sweetenham: Yeah, I agree. Thanks, Marc. I think that's a great summary. And it's particularly exciting to me that the investigators were able to achieve this kind of level of response and progression-free survival with a subcutaneous treatment. It's really quite remarkable and really exciting to see that.  We're going to wind up with our final abstract today, which is looking at the utilization of circulating tumor DNA in, again, in patients with aggressive B cell lymphoma. This is Abstract 7523, so maybe you could walk us through this one, Marc.  Dr. Marc Braunstein: Absolutely. So this is a poster being presented by Dr. Herrera looking at a, I guess you could call it a biomarker in the blood using circulating tumor DNA in patients with newly diagnosed diffuse large B cell lymphoma in the POLARIX study. So the results of the phase 3 POLARIX study were published last year in the New England Journal of Medicine and showed improvement in progression-free survival with the addition of these anti-CD79b antibody polatuzumab to standard R-CHOP chemotherapy compared to R-CHOP alone. And this study actually led to the approval of first-line treatment that includes polatuzumab.   In the abstract being presented by Dr. Herrera, the investigators looked at the value of circulating tumor DNA as a potential marker to serve as a guide for prognosis and predicting longer-term responses, particularly when the blood is cleared of circulating tumor DNA. So the study involved 654 patients who had ctDNA results both at baseline and then with longitudinal assessment, and they used an assay called the CAPP-Seq assay to assess circulating tumor DNA and assess for its clearance. In the study, undetectable circulating tumor DNA was achieved in 57% of patients who got the polatuzumab R-CHP combination and 59% of the patients who got R-CHOP by cycle 5 and then 6% in the polatuzumab group at 67% in the R-CHOP group.  So the rates of circulating tumor DNA clearance were similar between the 2 arms. But what's notable is that patients in the polatuzumab arm who achieved a complete response at the end of treatment plus cleared their circulating tumor DNA had superior progression-free and overall survival compared to patients who achieved a CR but retained circulating tumor DNA in their blood.   And this has implications because it might help gauge, for example, if patients may need additional cycles to clear the circulating tumor DNA, although we still need more data to answer whether that's necessary or not. And it may help serve as a predictive marker for longer-term remission, particularly in patients who perhaps have higher risk factors at baseline. So I don't think this is necessarily ready for primetime to use in clinical practice, but it is intriguing to know that we could finally have a tumor-specific biomarker in the blood to help monitor patients and potentially predict their longer-term remissions.  Dr. John Sweetenham: Thanks, Marc. I agree. Great summary, and obviously there's still something to learn about the kinetics of the response and so on. And also, I suppose it raises the question of whether those patients who still have detectable levels should be switched at the end of therapy to some kind of preemptive second-line therapy. And these are obviously all questions for the future, but it's going to be very interesting to watch this space, I think, and see how this story develops. Dr. Marc Braunstein: Absolutely. And my colleagues in the solid tumor space are already using circulating tumor DNA, for example, in colon cancer, to help with surveillance. So perhaps this could be a tool to use to predict relapse also in patients who are on surveillance after their treatment. But again, as you alluded to, we need more data to address that.  Dr. John Sweetenham: Well, thanks so much, Marc, for sharing your insights with us today on a really interesting set of abstracts coming up at the June meeting. And thanks for joining us on the ASCO Daily News Podcast. Dr. Marc Braunstein: Thank you for inviting me.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in a transcript of this episode. Join us again after the annual meeting for key takeaways on the late-breaking abstracts and other key advances from the ASCO Annual Meeting. And 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 speakers:  Dr. John Sweetenham 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 OncologyResearch Funding (Institution): Janssen, Celgene/BMS

Featuring perspectives from Drs Alexey Danilov, Matthew Davids, Lindsey Roeker, Philip Thompson and Prof Dr Arnon Kater, including the following topics: Front-Line Treatment of Chronic Lymphocytic Leukemia (CLL)   Introduction (0:00) Cases: A man in his early 90s with Rai Stage 0 CLL who underwent surveillance x 5 years and now develops cytopenias and transfusion-dependent anemia, and a woman in her late 60s with IGHV-unmutated CLL who develops night sweats, rapid doubling time of ALC — Bhavana (Tina) Bhatnagar, DO and Jennifer L Dallas, MD (3:18) Case: A man in his mid 50s with relapsed CLL after ibrutinib x 5 years now with disease progression — Amany R Keruakous, MD, MS (9:11) Dr Danilov presentation (16:47) Novel Strategies Combining Bruton Tyrosine Kinase (BTK) and Bcl-2 Inhibitors for CLL   Case: A man in his late 70s with IGHV-unmutated CLL under observation for many years who develops B symptoms, cytopenias and lymphadenopathy — Henna Malik, MD (32:15) Prof Kater presentation (37:18) Optimal Management of Adverse Events with BTK and Bcl-2 Inhibitors; Considerations for Special Patient Populations  Case: A man in his early 70s with multiple musculoskeletal comorbidities and transportation limitations develops symptomatic IGHV-mutated CLL with cytopenias — Syed F Zafar, MD (51:08) Cases: A man in his mid 50s with del(17p) CLL and significant lymphadenopathy and B symptoms who receives acalabrutinib and a woman in her early 70s with IGHV-mutated CLL and a complex karyotype — Dr Keruakous and Spencer H Bachow, MD (55:10) Dr Davids presentation (1:03:01) Selection and Sequencing of Available Therapies for Relapsed/Refractory Disease   Case: A man in his mid 70s with relapsed del(17p) CLL after ibrutinib with multiple chronic low-grade toxicities — Dr Bhatnagar (1:16:23) Dr Thompson presentation (1:20:56) Promising Investigational Agents and Strategies  Case: A woman in her late 70s with CLL (p53, 11q, 13q mutations), disease progression on ibrutinib and a BTK C481S mutation detected on repeat testing — Dr Bachow (1:39:09) Case: A man in his late 70s who develops Richter's transformation while receiving obinutuzumab/venetoclax for CLL — Justin Peter Favaro, MD, PhD (1:43:12) Dr Roeker presentation (1:48:29) CME information and select publications

Featuring perspectives from Dr Jeff Sharman, including the following topics: Introduction (0:00) Case: A man in his late 50s with progressive small lymphocytic lymphoma who developed acalabrutinib-associated rash — Shams Bufalino, MD (22:14) Case: A man in his late 60s with recurrent deep-vein thrombosis who is receiving warfarin and is diagnosed with chronic lymphocytic leukemia (CLL) requiring treatment — Shaachi Gupta, MD, MPH (27:27) Case: A man in his early 70s with IGHV-unmutated CLL who has severe cardiac disease requiring a defibrillator — Rajalaxmi McKenna, MD (34:45) Case: A man in his early 70s with CLL who remains in remission after treatment with chlorambucil/obinutuzumab — Philip L Brooks, MD (40:43) Case: A man in his early 50s with IGHV-unmutated CLL and del(17p) who developed atrial fibrillation on ibrutinib — Vignesh Narayanan, MD (45:03) Case: A woman in her late 80s with CLL transformed to Hodgkin lymphoma — Spencer H Bachow, MD (51:46) Case: A man in his late 50s with relapsed IGHV-mutated CLL who experienced acalabrutinib-associated headache — Erik Rupard, MD (56:22) Case: A woman in her mid 60s with IGHV-unmutated CLL and hemolytic anemia — Joanna Metzner-Sadurski, MD (1:01:38) CME information and select publications

Featuring perspectives from Dr Susan O'Brien, including the following topics: Introduction (0:00) Case: A woman in her mid 60s with relapsed Chronic Lymphocytic Leukemia (CLL) who experiences severe headaches on acalabrutinib — Bhavana (Tina) Bhatnagar, DO (12:57) Case: A man in his early 70s with IGHV-unmutated relapsed CLL — Gurveen Kaur, MD (24:43) Case: A man in his late 60s with chronic kidney disease and CLL who develops metastatic rectal cancer while receiving acalabrutinib — G Richard Polkinghorn, MD (31:11) Case: A woman in her mid 60s with relapsed CLL suspicious for Richter's transformation; Del(13q), TP53 and BTK resistance mutation — John N Allan, MD (35:18) Case: A woman in her mid 20s with CLL and transfusion-dependent autoimmune myelofibrosis — Amanda Blackmon, DO, MS (48:47) Journal Club with Susan O'Brien, MD (53:07) CME information and select publications

Featuring perspectives from Dr Jennifer Brown, including the following topics:  Introduction (0:00) Case: A man in his late 60s with chronic lymphocytic leukemia (CLL) on observation for 10 years who develops angioedema — G Richard Polkinghorn, MD (9:11) Case: A woman in her early 60s with small lymphocytic leukemia and BTK (Bruton tyrosine kinase)-related arthralgia — Rajni Sinha, MD, MRCP (13:57) Case: A man in his late 60s with CLL and hypertension, coronary artery disease, GERD and atrial fibrillation — Khuda Dad Khan, MD, PhD (22:29) Case: A man in his mid 60s with CLL who receives obinutuzumab and venetoclax — Raman Sood, MD (25:30) Case: A man in his early 70s with IGHV-mutated CLL — Gurveen Kaur, MD (34:36) Case: A man in his early 70s with CLL, thrombocytopenia and possible underlying plasma cell dyscrasia — Bhavana (Tina) Bhatnagar, DO (48:05) CME information and select publications

Featuring perspectives from Dr Kerry Rogers, including the following topics: Introduction (0:00) Hairy Cell Leukemia (2:30) Case: A man in his late 50s with newly diagnosed chronic lymphocytic leukemia (CLL) with an IGHV mutation — Jeanne Palmer, MD (17:01) Case: A woman in her mid 60s under observation for CLL for 6 years who now presents with worsening symptoms — Alexey V Danilov, MD, PhD (24:46) Case: A man in his mid 70s with multiple regimen-relapsed CLL, complex karyotype — Dr Danilov (34:31) Case: A man in his late 70s with newly diagnosed CLL and significant neutropenia — Amany R Keruakous, MD, MS (50:34) Case: A woman in her mid 60s with relapsed CLL who experiences severe headaches on acalabrutinib — Bhavana (Tina) Bhatnagar, DO (54:35) CME information and select publications

Featuring perspectives from Prof Peter Hillmen, including the following topics: Introduction (0:00) Case: A man in his early 60s with chronic lymphocytic leukemia (CLL) and Richter's transformation to Hodgkin lymphoma — Amanda Blackmon, DO, MS (2:05) Case: A man in his mid 70s with relapsed CLL after 3 years of second-line ibrutinib — Jeanne Palmer, MD (12:18) Case: A man in his early 50s with newly diagnosed IGHV-unmutated CLL — Del(17p), TP53 mutation — Alexey V Danilov, MD, PhD (21:26) Case: A woman in her early 50s who presents with persistent lymphocytosis — Rajalaxmi McKenna, MD (29:03) Case: A man in his late 50s with CLL who receives FCR and remains in complete remission 5 years later — Dr Blackmon (37:39) Case: A man in his early 70s with relapsed CLL who is concerned about contracting COVID-19 — Dr Danilov (44:11) Journal Club with Peter Hillmen, MB ChB, PhD (56:01) CME information and select publications

Guest: John C. Byrd, MD For patients with chronic lymphocytic leukemia, molecular analysis can provide critical information. Dr. John C. Byrd discusses the importance of IGHV and TP53 sequencing and the clinical value they provide.

Featuring an interview with Professor Dr Arnon Kater, including the following topics: Novel agents and their use in combination therapies for chronic lymphocytic leukemia (CLL) (0:00) Case: A man in his late 70s with complex karyotype CLL with deletion 17p and a TP53 mutation (37:27) Case: A man in his early 50s with del(13q) and IGHV-mutated CLL treated with venetoclax/ibrutinib (44:24) Case: A woman in her early 70s with del(13q), del(17p) CLL with a TP53 mutation treated with ibrutinib monotherapy (47:18) CME information and select publications

Featuring perspectives from Drs Jeff Sharman, Mitchell Smith and Philip Thompson, including the following topics: Treatment of CLL in 2021 Introduction (0:00) First-line therapy for a younger and fit patient with CLL (11:52) Case: A man in his mid-60s with IGHV-unmutated CLL — Mitchell R Smith, MD, PhD (16:20) Case: A man in his mid-30s with IGHV-unmutated CLL — Philip A Thompson, MD, BS (20:24) Case: A woman in her late 60s with IGHV-mutated, trisomy 12, TP53 wild-type CLL — Jeff Sharman, MD (25:11) First-line therapy for older and frail patients with CLL (26:55) Case: A man in his early 70s with IGHV-unmutated CLL — Dr Thompson (31:04) First-line therapy for patients with high-risk CLL (33:37) Choice of Bruton tyrosine kinase (BTK) inhibitor for the treatment of CLL (36:02) Prevention and management of COVID-19 in patients with CLL (43:21) Future Treatment of CLL Future role of BTK inhibitors combined with venetoclax in the management of CLL (48:33) Future role of pirtobrutinib (LOXO-305) in the management of CLL (52:22) Case: A woman in her late 60s with multiregimen-relapsed CLL — Dr Sharman (55:10) Case: A woman in her mid-50s with multiregimen-relapsed CLL — Dr Thompson (57:32) CME information and select publications

Featuring perspectives from Dr John M Pagel and Ms Lesley Camille Ballance, including the following topics: Introduction (0:00) The recent history of CLL treatment (2:09) Bruton tyrosine kinase (BTK) inhibitors (19:35) Case: A woman in her early 50s with previously untreated CLL who receives acalabrutinib — Lesley Camille Ballance, MSN, FNP-BC (23:31) Key data sets on BTK inhibitors in CLL (38:04) Case: A woman in her mid-40s with CLL who was initially observed off treatment — Ms Ballance (41:55) Case: A man in his early 60s with favorable-risk, IGHV-mutated CLL — 13q deletion — Ms Ballance (47:49) Case: A woman in her early 70s with multiregimen-relapsed CLL — Ms Balance (51:55) Key data sets on emerging therapies for CLL (54:01) CME information and select publications

Featuring a roundtable discussion with Ms Amy Goodrich and Drs Gigi Chen, Ilya Glezerman, Dipti Gupta, Yanjun Ma and Anthony R Mato, including the following topics: Case: A man in his mid-50s with treatment-naïve chronic lymphocytic leukemia (CLL) with no IGHV mutation begins therapy with venetoclax/obinutuzumab and develops tumor lysis syndrome (TLS) after cycle 1 of obinutuzumab — Anthony R Mato, MD, MSCE (0:00) Assessing patients with CLL for risk of TLS; use of antihyperuricemic agents (rasburicase and allopurinol) in the management of TLS associated with venetoclax/obinutuzumab (7:21) Selection of first-line therapy for patients with CLL (16:33) Perspective on the choice of Bruton tyrosine kinase (BTK) inhibitors versus venetoclax/obinutuzumab as up-front therapy (21:10) Results of the Phase III ELEVATE-RR study evaluating acalabrutinib versus ibrutinib for patients with previously treated, high-risk CLL; key findings from the ALPINE study comparing zanubrutinib to ibrutinib for relapsed CLL (24:01) GLOW: A Phase III trial of ibrutinib and venetoclax for untreated CLL/small lymphocytic lymphoma; efficacy and tolerability of LOXO-305 (pirtobrutinib) for CLL (29:44) Case: A man in his mid-40s with treatment-naïve CLL with an IGHV mutation receives venetoclax/obinutuzumab and develops neutropenia — Dr Mato (34:08) Treatment of neutropenia associated with venetoclax/obinutuzumab (38:11) Monitoring and management of renal dysfunction related to venetoclax-based regimens (44:23) Case: A man in his mid-60s with relapsed/refractory CLL who experiences disease progression on ibrutinib starts therapy with venetoclax/rituximab and develops biochemical TLS — Dr Mato (48:44) Pathophysiology of TLS; laboratory and clinical criteria for identifying patients at risk (51:30) Recommendations for mitigating the risk associated with TLS; real-world data on risk and prophylaxis (1:00:42) Efficacy and tolerability of febuxostat, allopurinol or rasburicase for the prevention and management of TLS (1:05:13) Case: A woman in her late 80s with relapsed/refractory CLL and underlying renal disease receives venetoclax monotherapy — Dr Mato (1:10:07) Case: A man in his early 60s with CLL develops atrial fibrillation after first-line therapy with ibrutinib — Dr Mato (1:23:30) Management of atrial fibrillation associated with ibrutinib (1:25:13) Evaluation of patients with atrial fibrillation; perspective on switching BTK inhibitors for those who develop cardiac adverse events (1:33:29) Cardiac side effects of BTK inhibitors; hypertension and ventricular arrythmias associated with ibrutinib (1:37:57) Incidence, risk factors and treatment of atrial fibrillation and bleeding related to ibrutinib (1:44:28) CME information and select publications

Proceedings from the second in a series of 11 summer webinars held following the 2021 ONS Annual Congress. Featuring perspectives from Ms Kristen E Battiato and Dr Jennifer Woyach, including the following topics: Introduction (0:00) Up-Front Treatment with a Bruton Tyrosine Kinase (BTK) Inhibitor for Patients with Chronic Lymphocytic Leukemia (CLL) Case: A man in his mid-70s with immunoglobulin heavy chain variable (IGHV)-unmutated CLL —Jennifer Woyach, MD (9:58) Case: A woman in her early 50s with IGHV-unmutated CLL/small lymphocytic lymphoma (SLL) and progressive lymphadenopathy — Kristen E Battiato, AGNP-C (22:20) First-Line Treatment with Obinutuzumab/Venetoclax for Patients with CLL Case: A woman in her late 60s with IGHV-mutated CLL — Trisomy 12 — Dr Woyach (30:16) Case: A man in his late 50s with IGHV-unmutated CLL/SLL, multifocal adenopathy and splenomegaly — Ms Battiato (36:09) Future Directions in CLL (U2 Regimen, LOXO-305, CAR T-Cell Therapy) Case: A man in his mid-80s with relapsed CLL and an acquired C418S BTK mutation associated with ibrutinib resistance — Dr Woyach (49:59) Case: A woman in her late 80s with relapsed CLL/SLL — 17p deletion, no IGHV mutation — Ms Battiato (52:06) NCPD information and select publications

In this episode,William G. Wierda, MD, PhD, Jeremy S. Abramson, MD, MMSc, and Brian Hill, MD, PhD, answer questions focused on personalizing therapy for patients with CLL considering patient characteristics and currently available clinical evidence.Presenters:William G. Wierda, MD, PhD, Program DirectorProfessor of MedicineChief, Section of CLLDepartment of LeukemiaThe University of Texas MD Anderson Cancer CenterHouston, TexasJeremy S. Abramson, MD, MMScAssociate ProfessorDepartment of MedicineHarvard Medical SchoolDirector, Center for LymphomaMassachusetts General HospitalBoston, MassachusettsBrian Hill, MD, PhDDirector, Lymphoid Malignancies ProgramTaussig Cancer InstituteCleveland ClinicCleveland, OhioContent based on an online CME program supported by educational grants from AstraZeneca; Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; and Lilly.Link to full program, including associated downloadable slidesets:http://bit.ly/3mLjeIb

Featuring perspectives from Dr Jennifer Woyach on the following topics: Practical considerations in treatment of CLL for practicing clinicians — Jennifer Woyach, MD (0:00) Case: A man in his early 60s with CLL with an IGHV mutation and deletion 13q receives ibrutinib/obinutuzumab on the control arm of the ECOG-EA9161 trial (26:25) Case: A man in his mid-70s with relapsed/refractory CLL (30:45) Case: A woman in her late 60s initially diagnosed with CLL with deletion 17p but no IGHV mutation undergoes Richter’s transformation (32:03) Biomarker assessment to guide treatment selection in CLL (46:30) Management of treatment-naïve CLL (52:42) Treatment options for relapsed/refractory CLL CME information and select publications (1:25:14) CME information and select publications

Featuring an interview with Dr John M Pagel about recently published and emerging research in the front-line treatment of chronic lymphocytic leukemia, including the following topics: New treatment paradigms in chronic lymphocytic leukemia (CLL) — John M Pagel, MD, PhD (00:00) Case: A man in his late 50s with treatment-naïve CLL and a history of hypertension and deep vein thrombosis (27:17) Case: A man in his mid-70s with treatment-naïve CLL harboring del(17p) and unmutated IGHV and a history of mild chronic kidney disease (29:26) Case: A man in his late 70s with multiple comorbidities is diagnosed with CLL with a TP53 mutation (31:09) CME information and select publications

In this episode, Jeff P. Sharman, MD, Danielle M. Brander, MD, and Nicole Lamanna, MD, answer questions focused on the optimizing BTK inhibitor therapy for previously untreated patients with CLL considering presentation characteristics and drug pharmacology.Presenters:Jeff P. Sharman, MD, Program DirectorMedical DirectorHematology ResearchUS Oncology ResearchEugene, OregonDanielle M. Brander, MDAssistant Professor of MedicineDivision of Hematologic Malignancies & Cellular TherapyDepartment of MedicineDuke UniversityAttending Physician, Hematologic MalignanciesDuke University Health SystemDurham, North CarolinaNicole Lamanna, MDAssociate AttendingLeukemia ServiceDirector of CLL ProgramHematologic Malignancies SectionDepartment of MedicineNew York-Presbyterian/Columbia University Medical Center New York, New YorkContent based on an online CME program supported by an educational grant from AstraZeneca.Link to full program, including associated downloadable slidesets:https://bit.ly/3hATX0L

Proceedings from Part 1 of a 2-part satellite symposia series during the 61st ASH Annual Meeting. Featuring perspectives from Dr Jeremy Abramson, Dr Bruce D Cheson, Prof John G Gribben, Dr Brad S Kahl, Dr Loretta Nastoupil and Dr Laurie H Sehn. Introduction Program Overview: Dr Love (00:00) Evolving Therapeutic Algorithms for Patients with Treatment-Naïve Chronic Lymphocytic Leukemia (CLL) Case (Dr Khan): A man in his late 40s with IGHV-mutated CLL who achieves a complete remission with first-line FCR but experiences multiple toxicities (01:26) Case (Dr Peswani): A man in his late 70s who presents with highly symptomatic CLL requiring an immediate response to treatment (10:36) Faculty Presentation: Dr Kahl (18:19) Management of Relapsed/Refractory (R/R) CLL and Novel Investigational Approaches Case (Dr Kale): A woman in her late 70s with small lymphocytic lymphoma who is hospitalized for the initial cycles of venetoclax/obinutuzumab because of poor renal function (31:50) Case (Dr Lamar): A man in his early 70s with CLL who receives ibrutinib and develops atrial fibrillation and hematuria requiring dose reduction (39:25) Faculty Presentation: Prof Gribben (46:38) Contemporary Management of Newly Diagnosed and R/R Follicular Lymphoma (FL) Case (Dr Kale): A man in his mid-70s with Stage III FL and multiple comorbidities who experiences a prolonged response to rituximab monotherapy (1:00:14) Additional questions from the community oncologist/hematologist panel regarding the management of FL (1:03:34) Faculty Presentation: Dr Cheson (1:12:05) Protocol and Off-Protocol Care for Patients with Mantle Cell Lymphoma (MCL) Case (Dr Peswani): A man in his early 70s who is diagnosed with MCL with gastrointestinal involvement (1:24:13) Additional questions from the community oncologist/hematologist panel regarding the management of MCL (1:28:31) Faculty Presentation: Dr Abramson (1:33:51) Recent Breakthroughs and Other Promising Approaches in the Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) Case (Dr Brenner): A woman in her mid-80s with DLBCL and a performance status of 2 who receives R-mini-CHOP but experiences disease progression after 4 months (1:47:02) Case (Dr Morganstein): A man in his early 60s with triple-hit DLBCL (1:52:35) Faculty Presentation: Dr Sehn (1:55:18) Integration of CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy into the Management of Lymphomas Questions from the community oncologist/hematologist panel regarding CAR T-cell therapy (2:08:34) Case (Dr Morganstein): A man in his early 40s with DLBCL who receives CAR T-cell therapy after no response to up-front R-CHOP and disease progression after salvage chemotherapy followed by ASCT (2:13:19) Faculty Presentation: Dr Nastoupil (2:16:08) CME information and select publications

Chronic Lymphocytic Lymphoma, Issue 2, 2019 — Part 1: Our interview with Prof Stilgenbauer highlights the following topics as well as cases from his practice: Updated International Workshop on Chronic Lymphocytic Leukemia guidelines for diagnosis, indications for treatment, response assessment and management of chronic lymphocytic leukemia (CLL) (00:00) Genetic abnormalities in CLL; effects of p53 mutations and 17p deletion on prognosis and therapy (02:48) Design and eligibility for the Phase III CLL14 trial of venetoclax/obinutuzumab versus chlorambucil/obinutuzumab for patients with previously untreated CLL and coexisting medical conditions (05:42) Recent data from the Phase III iLLUMINATE, Alliance A041202 and ECOG-E1912 trials comparing ibrutinib-based regimens to chemoimmunotherapy as first-line treatment for patients with CLL (07:51) Results from the CLL14 trial comparing venetoclax to chlorambucil as an addition to fixed-duration obinutuzumab therapy for CLL (10:17) Management of disease relapse on the CLL14 trial; role of minimal residual disease (MRD) assessment in therapeutic decision-making (13:19) Dosing and administration of the recently FDA-approved first-line regimen of venetoclax and obinutuzumab; mitigation of risk for tumor lysis syndrome (16:03) Mechanism of action of venetoclax; role of renal function in the decision to administer this agent (17:02) Emerging data with the combination of ibrutinib or venetoclax with anti-CD20 antibodies (20:05) Del(17p) and/or p53 mutation status and the selection of therapy for patients with CLL (22:09) Role of bendamustine/rituximab in the management of CLL (26:43) Perspective on the efficacy of venetoclax/obinutuzumab versus ibrutinib as first-line therapy for patients with CLL (28:38) Case: A man in his mid-60s with del(17p) CLL and no IGHV mutation experiences a dramatic response to first-line ibrutinib (30:42) Prolonged lymphocytosis during ibrutinib therapy (33:20) Clonal evolution in CLL; importance of monitoring for del(17p) and p53 mutations before treatment initiation (35:35) Sequencing of ibrutinib and venetoclax for patients with CLL; tolerability and quality of life with ibrutinib versus venetoclax (36:59) Management of arthralgias associated with Bruton tyrosine kinase (BTK) inhibitors (40:25) Case: A woman in her mid-70s with del(13q) CLL and no IGHV mutation receives acalabrutinib after experiencing disease progression on multiple lines of therapy, including ibrutinib (42:15) BTK inhibitor-associated headaches and atrial fibrillation (44:18) Efficacy of ibrutinib versus acalabrutinib; ongoing Phase III ACE-CL-006 study comparing acalabrutinib to ibrutinib for previously treated, high-risk CLL (47:31) Case: A man in his late 70s with del(11q) CLL and no IGHV mutation attains a complete response and MRD-negative status with venetoclax and obinutuzumab on the Phase III CLL14 trial (51:59) Side effects of venetoclax/obinutuzumab (53:36) Case: A man in his early 70s with hairy cell leukemia (HCL) and a BRAF mutation experiences disease progression after receiving vemurafenib as second-line therapy (57:25) Activity and tolerability of the recently FDA-approved antibody-drug conjugate moxetumomab pasudotox-tdfk in patients with relapsed/refractory HCL (59:10) Novel approaches under investigation for HCL (1:01:11) Case: A woman in her late 50s develops Richter’s transformation (RT) from CLL to diffuse large B-cell lymphoma (DLBCL) after receiving ibrutinib as second-line therapy (1:03:52) Pathogenesis and frequency of RT in patients with relapsed/refractory CLL (1:06:45) Comparison of the biology of Richter’s transformed versus de novo DLBCL; novel therapies under investigation for RT (1:10:06) CME information and select publications  

Chronic Lymphocytic Lymphoma, Issue 2, 2019 — Part 2: Our interview with Dr Woyach highlights the following topics as well as cases from her practice: Recent data and evolution of the front-line treatment paradigm for patients with CLL (00:00) Evaluation of MRD and implications for therapy (03:50) Efficacy and tolerability of first-line regimens for CLL (06:14) Perspective on the role of chemoimmunotherapy for patients with CLL (08:41) Case: A woman in her mid-70s experiences a dramatic response after receiving ibrutinib as first-line therapy for CLL (10:48) Bleeding and arthralgias associated with ibrutinib (12:14) Rates of discontinuation and the role of dose reduction to mitigate side effects in patients receiving ibrutinib (14:45) Incidence and management of opportunistic infections during ibrutinib treatment (18:11) Role of chimeric antigen receptor (CAR) T-cell therapy in CLL; effect of ibrutinib on CAR T-cell generation and efficacy (21:54) Case: A man in his late 60s with CLL receives acalabrutinib on a clinical trial after developing atrial fibrillation on ibrutinib therapy (24:01) Therapeutic approach for patients who develop resistance to BTK inhibitors (27:19) Understanding the C481S mutation as a mechanism of resistance to ibrutinib and acalabrutinib (30:47) Targeting the C481S mutation to overcome resistance to BTK inhibitors (32:06) Case: A woman in her mid-60s with del(17p) CLL and no IGHV mutation receives venetoclax after disease progression on multiple lines of therapy (36:11) Prophylactic measures to prevent venetoclax-associated tumor lysis syndrome (38:25) Emerging data with the combination of ibrutinib and venetoclax for CLL (40:04) Activity and tolerability of PI3 kinase inhibitors for patients with CLL (44:17) Acalabrutinib with obinutuzumab for treatment-naïve and relapsed/refractory CLL (47:51) Incidence and spectrum of second cancers among patients with CLL receiving BTK inhibitors (49:51) Case: A man in his early 70s develops RT to DLBCL after receiving ibrutinib as first-line therapy for CLL (51:00) Prognosis and management of RT (53:38) Role of immune checkpoint inhibitors and CAR T-cell therapy in the management of RT (56:37) Ongoing Phase III EA9161 and Alliance A041702 studies evaluating the addition of venetoclax to ibrutinib with obinutuzumab for patients with CLL (59:21) CME information and select publications  

Chronic Lymphocytic Leukemia Update, Issue 1, 2019 — Part 2: Our most recent one-on-one interview with Dr Mato featuring emerging research and cases from his practice: Emerging data and recent advances in the management of CLL (00:00) Perspective on the role of MRD assessment in therapeutic decision-making (03:13) Duration of therapy for patients with CLL; integration of venetoclax into the treatment algorithm (05:44) Available data with the addition of rituximab or obinutuzumab to novel therapies (08:07) Selection of patients with CLL for treatment with FCR (fludarabine/cyclophosphamide/rituximab) (11:44) Novel combination approaches to limiting the duration of therapy for patients with CLL (13:36) Spectrum and incidence of toxicities with ibrutinib/venetoclax compared to either agent alone (15:41) Therapeutic options for patients with CLL in the first-line setting (17:55) Safety profile and quality of life with venetoclax versus ibrutinib (19:37) Frequency of and reasons for discontinuation of therapy with ibrutinib (22:37) Left atrial abnormality as a predictor of ibrutinib-associated atrial fibrillation in patients with CLL (24:48) Real-world outcomes and management strategies for patients with venetoclax-treated CLL in the United States (27:04) Experience conducting real-world outcome studies (29:06) Role of chemoimmunotherapy in the management of relapsed/refractory CLL (31:24) Clinical experience with and management of ibrutinib-associated adverse events (33:21) Investigation of ibrutinib in combination with CAR T-cell therapy for CLL (37:37) Case: A woman in her mid-70s with del(17p) CLL and no IGHV mutation experiences arthralgia and hypertension during second-line therapy with ibrutinib (40:53) Incidence and management of hypertension associated with ibrutinib (42:52) Dose reductions of ibrutinib to mitigate side effects; effect on efficacy (46:21) Case: A man in his mid-60s with a history of hypertension and atrial fibrillation receives acalabrutinib as first-line therapy for CLL (49:08) Headaches and hypertension associated with acalabrutinib (50:20) Comparative efficacy and spectrum of kinase activity with ibrutinib, acalabrutinib and zanubrutinib (52:38) Activity and tolerability of acalabrutinib versus ibrutinib (54:38) Case: A woman in her mid-50s with von Willebrand disease and CLL receives venetoclax after experiencing disease progression through several lines of therapy (56:58) Dose adjustments of venetoclax and management of TLS (1:01:18) Case: A woman in her late 80s with del(13q) CLL with IGHV mutation, symptomatic anemia and lymphadenopathy receives first-line obinutuzumab (1:04:19) Clinical experience with obinutuzumab-associated infusion-related reactions (1:06:26) Choice of first-line therapy for older patients with CLL (1:08:34) CME information and select publications  

Chronic Lymphocytic Leukemia Update, Issue 1, 2019 — Part 1: Our most recent one-on-one interview with Dr Wierda featuring emerging research and cases from his practice: Evolution of the treatment paradigm for patients with chronic lymphocytic leukemia (CLL) (00:00) Biomarker assessment for patients with newly diagnosed CLL (03:27) Therapeutic approach for older patients with CLL; IGHV mutation status in treatment decision-making (06:41) Case: A woman in her early 70s with CLL with deletion 17p, a p53 mutation and no IGHV mutation achieves a complete remission with ibrutinib and venetoclax as first-line therapy on a clinical trial (10:40) Implications of del(17p) and p53 mutations in CLL pathogenesis and for the selection of treatment (12:03) Efficacy of venetoclax alone and in combination with obinutuzumab or rituximab (15:40) Phase II trial of ibrutinib with venetoclax for CLL (20:04) Ongoing Phase II CAPTIVATE trial of ibrutinib with venetoclax as front-line therapy (22:20) Relevance of minimal residual disease (MRD) as a clinical endpoint in CLL (24:54) Effect of MRD status on outcomes in the Phase III MURANO trial evaluating venetoclax with rituximab for relapsed/refractory CLL (28:02) Risk of tumor lysis syndrome (TLS) with venetoclax (32:02) Prophylactic approaches for TLS associated with venetoclax (35:00) Ongoing Phase III trial of ibrutinib and venetoclax; evaluation of ibrutinib/venetoclax in combination with an anti-CD20 antibody (37:02) Potential clinical role of ibrutinib/venetoclax for patients with CLL (41:27) Case: A man in his late 50s with idiopathic thrombocytopenic purpura and del(11q) CLL with no IGHV mutation receives acalabrutinib after multiple lines of therapy, including venetoclax and ibrutinib (43:23) Efficacy and side-effect profile of acalabrutinib versus ibrutinib (48:39) Results of the Phase III ASCEND study of acalabrutinib alone versus investigator’s choice of idelalisib/rituximab or bendamustine/rituximab for relapsed/refractory CLL (54:34) Ongoing Phase III ELEVATE-TN trial of acalabrutinib alone versus acalabrutinib/obinutuzumab versus chlorambucil/obinutuzumab for previously untreated CLL (56:14) Emerging data with next-generation, reversible Bruton tyrosine kinase inhibitors for CLL (1:00:34) Mechanism of action, efficacy and tolerability of the recently FDA-approved antibody-drug conjugate moxetumomab pasudotox-tdfk for relapsed/refractory hairy cell leukemia (1:02:24) Case: A woman in her early 60s with del(17p) CLL and no IGHV mutation receives venetoclax and obinutuzumab as first-line therapy (1:05:51) Activity and safety profile of chimeric antigen receptor (CAR) T-cell therapy for CLL (1:08:40) Challenges in the clinical management of CLL (1:13:29) CME information and select publications  

This week we look at the NEJM publication earlier this month (https://www.nejm.org/doi/full/10.1056/NEJMoa1817073) of E1912. Points of discussion include IGHV mutational status, PFS vs. OS as endpoints in CLL, the benefit of rituximab in addition to ibrutinib, and ibrutinib toxicity in younger vs. older CLL patients. (Also, apologies to my APPE student for dropping this Pod *after* your journal club on this paper.)

Video proceedings from the fourth in a series of 6 integrated symposia held at the 2019 ONS Annual Congress. Featuring perspectives from Dr Paul M Barr, Ms Josie Bazemore, Dr Nitin Jain and Ms Lynn Rich: Introduction (0m0s) Program overview: Dr Love Newly Diagnosed Chronic Lymphocytic Leukemia (CLL): Observation versus Treatment (00:38) Case (Ms Bazemore): A woman in her early 60s with CLL with del(17p) and an IGHV mutation who was observed for 1 year before beginning treatment with ibrutinib (2:17) First-Line Treatment of CLL (6:58) Case (Ms Rich): A woman in her late 30s with newly diagnosed CLL who received FCR and has developed multiple infections after the completion of treatment (15:52) Case (Ms Bazemore): A man in his early 90s with CLL with unmutated IGHV who experienced a complete response to first-line obinutuzumab/chlorambucil (48:40) Relapsed/Refractory CLL (53:33) Case (Ms Rich): A man in his early 70s with relapsed CLL and a high tumor burden who initiated treatment with venetoclax (1:12:24) Case (Ms Bazemore): A man in his mid-60s with relapsed CLL who was admitted to receive venetoclax because of concerns with compliance (1:15:40) Case (Ms Rich): A man in his mid-70s with heavily pretreated CLL who was referred for hospice but is currently faring well off treatment (1:22:09) Select publications

CLL, Chronic Lymphocytic Leukemia, What is the significance of IGHV mutations and how they are assessed.  Presented by Jennifer Brown, M.D., Ph.D., Director of the CLL Center and the Dana-Farber Cancer Institute.

CLL, Chronic Lymphocytic Leukemia, What is the significance of IGHV mutations and how they are assessed.  Presented by Jennifer Brown, M.D., Ph.D., Director of the CLL Center and the Dana-Farber Cancer Institute.