Podcasts about ighv

Featuring perspectives from Dr Kerry Rogers, moderated by Dr Stephen "Fred" Divers, including the following topics:  Chronic Lymphocytic Leukemia (CLL) — Dr Rogers (0:00) Case: A man in his mid 70s with CLL and a history of atrial fibrillation — Dr Lamar (13:08) Case: A fit man in his early 80s with IGHV-unmutated, TP53-mutant symptomatic CLL — Dr Mulherin (21:16) Case: A woman in her mid 80s with IGHV-mutated recurrent CLL who receives pirtobrutinib — Dr Warsch (32:41) Case: A woman in her late 70s with recurrent del(17p) CLL who receives venetoclax/obinutuzumab — Dr Yannucci (44:52) CE information and select publications

JCO Editor-in-Chief Dr. Jonathan Friedberg is joined by colleagues Dr. Jennifer Woyach, Dr. Wojciech Jurczak, and Dr. Matthew Davids to discuss simultaneous publications presented at ASH 2025 on pertibrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Jonathan Friedberg: I'm Jonathan Friedberg, editor of Journal of Clinical Oncology, and welcome to JCO After Hours, where we are covering two manuscripts that were presented at the American Society of Hematology meeting 2025 in Orlando, Florida. I am delighted to be joined by colleagues on this call to discuss these pivotal manuscripts which cover the topic of pirtobrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. I will first just introduce our guests, Dr. Woyach. Dr. Jennifer Woyach: Hi, my name is Jennifer Woyach. I am from the Ohio State University. Dr. Wojciech Jurczak: Hello, I am Wojciech Jurczak, working at the National Research Institute of Oncology in Krakow, Poland. Dr. Matthew Davids: Hi, I am Matthew Davids from Dana-Farber Cancer Institute in Boston. Dr. Jonathan Friedberg: We are going to start by just learning a little bit about these two trials that were both large, randomized phase 3 studies that I think answered some definitive questions. We will start with your study, Jennifer. If you could just describe the design of your study and the patient population. Dr. Jennifer Woyach: Absolutely. So this is the BRUIN CLL-314 study, and this is a phase 3 randomized trial of pirtobrutinib versus ibrutinib in patients with CLL or SLL who had not previously been treated with a covalent BTK inhibitor. The patients were both treatment-naive and relapsed/refractory, about one-third of the patients treatment-naive, the rest relapsed/refractory, and they were stratified based upon 17p deletion and the number of prior lines of therapy. The primary objective was looking at non-inferiority of overall response rate over the entire treated population as well as the relapsed/refractory patient population. Key secondary objectives included progression-free survival in the intention-to-treat and the smaller relapsed/refractory and treatment-naive populations. Dr. Jonathan Friedberg: And just comment a little bit on the risk of the patients. Dr. Jennifer Woyach: This study was fairly typical of this cohort of patients. Within the relapsed/refractory patient population, there was a median of one prior line of therapy in each of the groups, up to nine prior lines of therapy in the patients included on the study. For the overall cohort, about two-thirds of the patients were IGHV unmutated, about 15% had 17p deletion, 30% had TP53 mutations, and about 35% to 40% had a complex karyotype, which is three or more abnormalities. Dr. Jonathan Friedberg: And what were your findings? Dr. Jennifer Woyach: Regarding the primary outcome, which is the focus of the publication, we did find that pirtobrutinib was indeed non-inferior and actually superior to ibrutinib for overall response rate throughout the entire patient population and in both the relapsed/refractory and treatment-naive cohorts. PFS is a little bit immature at this time but is trending towards also being significantly better in pirtobrutinib-treated patients compared with ibrutinib-treated patients. Probably most significantly, we found this to be the case in the treatment-naive cohort where there was a striking trend to an advantage of pirtobrutinib versus ibrutinib. Dr. Jonathan Friedberg: And the follow-up that you have on that progression-free survival? Dr. Jennifer Woyach: So we have about 18 months follow-up on progression-free survival. Dr. Jonathan Friedberg: The second study, Wojciech, can you just go through the design and patient population that you treated? Dr. Wojciech Jurczak: Thank you, Dr. Friedberg, for this question. So the BRUIN CLL-313 study was, in fact, the first phase 3 study with pirtobrutinib in exclusively untreated CLL patients. It was a randomized study where we challenged pirtobrutinib versus bendamustine-rituximab. At the time we designed the protocol, bendamustine-rituximab was an option as a standard of care, and Bruton tyrosine kinase monotherapy was used far more commonly than nowadays. The primary target of the study was progression-free survival. We took all untreated patients except for those with 17p deletions. Therefore, it is a good representation for intermediate risk. We had about 60% of the population, 56 to be precise, which was unmutated, evenly distributed into two treatment arms. 17p deleted cases were excluded, but we had about 7% and 8% of TP53 mutated patients as well as about 11% and 7%, respectively, in the pirtobrutinib and bendamustine-rituximab arm of patients with complex karyotype. The progression-free survival was in favor of pirtobrutinib and was assessed by an independent review committee. What is important is that the progression-free survival of the bendamustine-rituximab arm was actually similar to the other studies addressing the same questions, like the comparison with ibrutinib in the ALLIANCE study or zanubrutinib in the SEQUOIA study. What was different was the hazard ratio. In our study, it was 0.20. It was one of the longest effect sizes noted in the frontline BTK study. It represented an 80% reduction in progression-free survival or death. If we compare it to ibrutinib or zanubrutinib, it was 0.39 and 0.42 respectively. Presumably, this great effect contributed towards a trend of overall survival difference. Although survival data are not mature enough, there is a clear trend represented by three patients we lost in the pirtobrutinib arm versus 10 patients lost in the bendamustine-rituximab arm. This trend in overall survival is becoming statistically significant despite the fact that there was a possibility of crossover, and effectively 52.9 patients, which means 18 out of 34 patients relapsing in the bendamustine-rituximab arm, were treated by pirtobrutinib. Dr. Jonathan Friedberg: I am going to turn it over to Matt. The question is: why study pirtobrutinib in this patient population? And then with these two studies, how do you find the patients that were treated, are they representative of people who you see? And do you see this maybe being approved and more widely available? Dr. Matthew Davids: I think in terms of the first question, why study this in a frontline population, we have seen very impressive data with pirtobrutinib in a very difficult-to-treat population of CLL patients. This was from the original BRUIN phase 1/2 study where most of the patients had at least two or three lines of therapy, often both a covalent BTK inhibitor and the BCL2 inhibitor venetoclax, and yet they were still responding to pirtobrutinib. The drug was also very well tolerated in that early phase experience. And actually, we have seen phase 3 data from the BRUIN 321 study comparing pirtobrutinib to bendamustine and rituximab in a relapse population as well. So I think that really motivated these studies to look at pirtobrutinib as a first therapy. You know, often in other cancers of course, we want to use our best therapy first, and I think these studies are an initial step at looking at that. In terms of the second question around the patient population, these are pretty representative patient populations, I would say, for most frontline CLL studies. We see patients who are a bit younger and fitter than sort of the general population of CLL patients who are treated in clinical practice, and I think that is true here as well. Median age in the sort of mid-60s here is a bit younger than the typical patients we are treating in practice. But that is not different from other CLL frontline studies that we have seen recently, so I think it makes it a little bit easier as we kind of think across studies to feel comfortable that these are relatively similar populations. Dr. Jonathan Friedberg: How do you see this either getting regulatory approval or potentially being used compared to current standard of care options? Dr. Matthew Davids: So my understanding is that both of these trials were designed with registrational intent in the frontline setting, and they are both positive studies. That is certainly very encouraging in terms of the potential for an approval here. We have seen in terms of the FDA recently some concerns around the proportion of patients who are coming from North America, and my understanding is that is relatively low on these two studies. But nonetheless, the datasets are very impressive, and so I think it is certainly supportive of regulatory approval for frontline pirtobrutinib. Dr. Jonathan Friedberg: I will ask Jennifer a question. The control arm in your study was ibrutinib, and I think many in the audience may recognize that newer, second-generation BTK inhibitors like acalabrutinib and zanubrutinib are more frequently used now if monotherapy is decided. How do you respond to that, and how would you put your results in your pirtobrutinib arm in context with what has been observed with those agents? Dr. Jennifer Woyach: Yeah, that is a great question. Even though in the United States we are predominantly using acalabrutinib or zanubrutinib when choosing a monotherapy BTK inhibitor, this is actually not the case throughout the entire world where ibrutinib is still used very frequently. The head-to-head studies of both acalabrutinib and zanubrutinib compared to ibrutinib have shown us pretty well what the safety profile and efficacy profile of the second-generation BTK inhibitors is. So even though we do not have a head-to-head study of acalabrutinib or zanubrutinib versus pirtobrutinib, I think, given the entirety of data that we have with all of the covalent BTK inhibitors, I think we can safely look at the pirtobrutinib arm here, how the ibrutinib arm compares or performs in context with those other clinical trials. And though we really can not say anything about pirtobrutinib versus acalabrutinib or zanubrutinib, I think we can still get a good idea of what might be the clinical scenarios in which you might want to choose pirtobrutinib. Dr. Jonathan Friedberg: And Wojciech, do you agree with that? Obviously, I think you have acknowledged that chemoimmunotherapy is rarely used anymore as part of upfront treatment for CLL. So, I guess a similar question. If you were to put the pirtobrutinib result in your study in context with, I guess, more contemporary type controls, would you agree that it is competitive? Dr. Wojciech Jurczak: Well, I think that that was the last study ever where bendamustine-rituximab was used as a comparator arm. So we should notice that smashing difference. Because if we look at the progression-free survival at two years, we have 93.4% in pirtobrutinib arm versus 70.7% in bendamustine-rituximab arm. Bendamustine-rituximab arm did the same as in the other trials, like ALLIANCE or SEQUOIA. Pirtobrutinib did exceptionally well, as pirto is not just the very best BTK inhibitor overcoming the resistance, but perhaps even more important for the first line, it is very well tolerated and is a very selective drug. Now, if we look at treatment-related adverse events, the discontinuation rate, they were hardly ever seen. If we compared the adverse events in exposure-adjusted incidence, literally all adverse events were two or three times higher in bendamustine-rituximab arm except for the bleeding tendency, which however was predominantly in CTCAE grade 1 and 2 with just 0.7% of grade 3 hemorrhage. Therefore, I think that we should actually put the best and the safest drugs upfront if we may, and pirtobrutinib is, or should be, the first choice if we choose monotherapy. Now, I understand that we are not presenting you the data of pirtobrutinib in combination with anti-CD20 or with BCL2 inhibitors, but that is to come. Dr. Jonathan Friedberg: Matt, how would you envision, were regulatory approval granted and this were an option, using this in the upfront patient population? Is there anybody who you would preferentially use this or start on this treatment? Or would this be something that you would tend to reserve for second line? Dr. Matthew Davids: So I would say that in general for most of my patients who would want to start with a continuous BTK inhibitor, I would still use a covalent BTK inhibitor, and I say that for a couple of reasons despite the very promising data from these studies. The first is that the follow-up for both of these phase 3 trials is still quite short, in the range of a median 18 to 24 months. And we know that CLL is a marathon, not a sprint, and these patients are going to probably be living for a very long time. And we do have much longer follow-up from the covalent BTK inhibitors, median of 10-year follow-up with ibrutinib and five to six years with zanubrutinib and acalabrutinib respectively. And you know, I do not think that the pirtobrutinib is going to fall off a cliff after two years, but on the other hand, I think there is a lot of value to long-term data in this disease, and that is why I think for most of my patients I would stick with covalent BTK inhibitors. But the other important factor that we need to consider is patients who are younger and may have many different CLL treatments over the years. We have to be very careful, I think, about how we sequence these drugs. We know right now that we can start with covalent BTK inhibitors and then subsequently patients will respond well to the non-covalent inhibitor pirtobrutinib in later lines of therapy. But right now we do not have prospective data the other way around. So how will the patients on these studies who progress on pirtobrutinib respond to covalent BTK inhibitors? We do not know yet. There have not been a lot of progression events, which is great, but we would like to see some data in that respect to feel more comfortable with that sequence. Now, I do think that particularly for older patients and those who have significant cardiovascular comorbidities, if they wanted to go on a continuous BTK inhibitor, I do think these data really strongly support using pirtobrutinib as the BTK inhibitor of choice in that population. In particular, the cardiovascular risks with pirtobrutinib seem to be quite low. I was very struck in the comparison with BR that the rate of AFib was equivalent between the two arms of the study. And that is really the first time we have seen that with any of these BTK inhibitors, no elevated risk of AFib in a randomized study. I think that is the population where it will get the most traction first, is the upfront, sort of older patient with significant cardiovascular comorbidities. And as the data from these studies mature, I think that we will start to see more widespread use of pirtobrutinib in the frontline setting. Dr. Jonathan Friedberg: Jennifer, I am just curious if you have any personal experience or heard anecdotally about after progression on pirtobrutinib the use of other BTK inhibitors and whether there is a growing experience there. Dr. Jennifer Woyach: I do not think that there is much clinical experience, you know, as Matt alluded to, it certainly has not been tested yet. There has been some data in relapsed CLL suggesting that in people who have resistance mutations to covalent BTK inhibitors after treatment with pirtobrutinib, sometimes those mutations go away. I think most of us are concerned that they are probably not actually gone but maybe in compartments that we just have not sampled, suggesting that sort of approach where you might sequence a covalent inhibitor after a non-covalent in somebody who had already been resistant probably would not work that well. But, you know, in this setting where people had never been exposed to a covalent BTK inhibitor before, we really have no idea what the resistance patterns are going to be like. We assume they will be the same as what we have seen in relapsed CLL, but I think we just need some longer follow-up to know for sure. Dr. Wojciech Jurczak: If I may confront Dr. Davids about the use of covalent BTK inhibitors upfront, well, I think that we should abandon the idea of using the first and the second and the third generation, at least if we don't have medical lines. If we endlessly block the same pathway, it is not going to be effective. So if pirtobrutinib gets approval in first, second line, we do not necessarily have to use it in the first line. I am not here in a position to defend that we should treat patients with pirtobrutinib upfront and not BCL2 time-limited regimen. However, the way I look at CLL patients when choosing therapy is not just how should I treat them now, but what would be the best regimen in 5, 10 years if I have to re-treat them. And in some instances, the idea may be that in this setting we would like to have a BTK inhibitor upfront to have a BCL2 inhibitor later to make it time-limited. Although I understand and I agree with Matthew that if we have an elderly, fragile population, then the charm of having a drug taken once a day in a tablet with literally few cardiovascular adverse events might be an option. Dr. Jonathan Friedberg: And I will give Matt the last word whether he wants to respond to that, and also just as a forward-looking issue, I know both investigators have implied that there will be future studies looking at combinations with pirtobrutinib, and if you have any sense as to what you would be looking for there. Dr. Matthew Davids: The field really is heading toward time-limited therapy for most patients, I would say. There is a bit of a discrepancy right now in the field between sort of what we are doing in academic practice and what is done sort of more widely in community practice. And so right now we are going to see evolving datasets comparing these approaches. We are already seeing data now from the CLL17 study with ibrutinib comparing continuous to time-limited venetoclax-based therapy, and we are seeing similar efficacy benefits from these time-limited therapies without the need for continuous treatment. And so that is where I think some of the future studies with pirtobrutinib combining it with venetoclax and other partners are so important. Fortunately, several of these studies are already ongoing, including a phase 3 trial called CLL18, which is looking at pirtobrutinib with venetoclax, comparing that to venetoclax and obinutuzumab. So I am optimistic that we are going to be developing these very robust datasets where we can actually use pirtobrutinib in the frontline setting as a time-limited therapy as a component of a multi-drug regimen. So far, those early data are very promising. Dr. Wojciech Jurczak: Perhaps last but not least, in a single center we have treated over 300 patients with pirtobrutinib. So eventually some of them relapsed. And I must say that our experience on BCL2 inhibitors, not just venetoclax but including sonrotoclax, are appealingly good. Therefore, by using pirtobrutinib even earlier, we do not block the efficacy of other compounds. Dr. Jonathan Friedberg: All right. Well, I want to thank all of our speakers. I also want to congratulate our two guests who presented these very influential papers at the ASH Annual Meeting, and chose to publish them in JCO, so we thank you for that, and Dr. Davids for your commentary - really appreciated. That is this episode of JCO After Hours. Thank you for your attention. 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.   Disclosures Dr. Wojciech Jurczak Consulting or Advisory Role: BeiGene, Lilly, Abbvie/Genentech, Takeda, Roche, AstraZeneca Research Funding: Roche, Takeda, Janssen-Cilag, BeiGene, AstraZeneca, Lilly, Abbvie/Genentech Dr. Jennifer Woyach Consulting or Advisory Role: Pharmacyclics, Janssen, AstraZeneca, Beigene, Loxo, Newave Pharmaceutical, Genentech, Abbvie, Merck Research Funding: Company name: Janssen, Schrodinger, beone, Abbvie, Merck, Loxo/Lilly Dr. Matthew Davids Honoraria: Curio Science, Aptitude Health, Bio Ascend, PlatformQ Health, Plexus Consulting or Advisory Role: Genentech, Janssen, Abbvie, AstraZeneca, Adaptive Biotechnologies, Ascentage Pharma, BeiGene, Lilly, Bristol-Myers Squibb, Genmab, Merck, MEI Pharma, Nuvalent, Inc., Galapagos NV, Schroedinger Research Funding: Ascentage Pharma, Novartis, MEI Pharma, AstraZeneca  

En este episodio del podcast de ACHO hematología, la Dra. Virginia Abello, hematóloga del CTIC en Bogotá, y el Dr. Luis Salazar, hematólogo de la Clínica Foscal Internacional en Bucaramanga, ambos de Colombia, abordan los avances más destacados en el tratamiento de la Leucemia Linfocítica Crónica (LLC) presentados en el congreso de la Asociación Europea de Hematología 2025. La dinámica gira en torno a la evolución del manejo de esta enfermedad, centrándose en terapias dirigidas, la importancia de la enfermedad medible residual (EMR), y la posibilidad de alcanzar tratamientos finitos e incluso hablar de curación en ciertos subgrupos de pacientes. Con un enfoque profundo, los ponentes analizan datos recientes de estudios clínicos clave como GAIA (CLL13), FLAIR, CAPTIVATE y AMPLIFY, reflexionando sobre el impacto de estos hallazgos en la práctica clínica actual y futura.Durante la conversación, se discutieron las estrategias emergentes de desescalonamiento terapéutico guiado por biomarcadores, el rol de la EMR como objetivo terapéutico y como potencial herramienta para suspender tratamientos de forma segura. Se destacaron los resultados de combinaciones libres de quimioterapia, como venetoclax con ibrutinib u obinutuzumab, las diferencias entre pacientes con biomarcadores de alto riesgo como IGHV no mutado o TP53 aberrado, y la relevancia de los inhibidores de BTK de nueva generación como acalabrutinib. La conclusión fue clara: tratar menos puede significar lograr más, siempre que sepamos identificar adecuadamente a qué pacientes aplicar estas estrategias, en qué momento y con qué herramientas de seguimiento clínico.Dentro de su conversación, se plantearon las siguientes preguntas:¿Cómo se pueden usar los biomarcadores para guiar el desescalonamiento del tratamiento en LLC?¿Qué nos mostró el estudio GAIA (CLL13) sobre la profundidad de la respuesta y su impacto en la progresión de la enfermedad?¿Cuáles son los beneficios y limitaciones del uso de la EMR como objetivo terapéutico?¿Qué diferencias observamos entre los pacientes con mutación del IGHV y los no mutados en los estudios analizados?¿Qué aprendimos del estudio CAPTIVATE sobre las terapias finitas y su efectividad a largo plazo?¿Qué aporta el estudio FLAIR en términos de comparación con la quimioinmunoterapia tradicional?¿Qué hallazgos nos deja el estudio AMPLIFY sobre el uso de acalabrutinib en combinación y su impacto en EMR?¿Cuáles son los retos actuales para aplicar estos avances en países latinoamericanos?¿Podemos hablar realmente de curación en LLC con las combinaciones actuales?¿Qué implicaciones clínicas tiene la cinética de la EMR en la toma de decisiones terapéuticas?¿Cómo debería cambiar la práctica clínica cotidiana frente a estos nuevos datos?¿Qué tipo de pacientes deberían aún recibir tratamientos continuos y por qué? Fecha de grabación: 20 de agosto de 2025.  Referencia:Este contenido se basa en la interpretación crítica de la evidencia científica disponible, así como en la experiencia clínica del o los ponentes como profesionales de la salud en instituciones de referencia.Para profundizar en los conceptos discutidos, se recomienda al profesional de la salud consultar literatura científica vigente, guías clínicas internacionales y la normatividad aplicable en su país.

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 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 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 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.