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This is Part 3 of Treatment Approaches to Relapsed/Refractory CLL: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Nicole Lamanna, John Allan, and Inhye Ahn discuss the third-line treatment of chronic lymphocytic leukemia (CLL). The patient in question originally presented with CLL with a white blood cell (WBC) count of 13 x 109/L and normal hemoglobin and platelets. She was observed for 4 years and then developed progressive disease with weight loss, splenomegaly, and lymphadenopathy. At this point, her WBC was 220 x 109/L, her hemoglobin was 9.4, and her platelet count was 102,000. Sequencing revealed unmutated IGHV, TP53 wildtype, deletion 13q, and trisomy 12. She was initially treated with acalabrutinib for 4 years but developed progressive disease, and then received venetoclax and rituximab for 2 years. She was monitored but developed progressive disease approximately 30 months off therapy, at age 74 years. In the conversation that follows, the faculty discuss potential third-line treatment options for this patient, whether she would be a candidate for CAR T-cell therapy if she were younger, whether venetoclax re-treatment would be an option, and more.
This is Part 2 of Treatment Approaches to Relapsed/Refractory CLL: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Nicole Lamanna, John Allan, and Inhye Ahn discuss second-line treatment strategies for chronic lymphocytic leukemia (CLL). The patient is a 71-year-old man who presented in 2014 with symptomatic CLL after being monitored for 4 years. He then developed progressive fatigue, organomegaly, and bulky lymph nodes. Sequencing revealed unmutated IGHV and deletion 11q. He was initially treated with ibrutinib at 420 mg daily and then developed progressive disease after 5 years. In the conversation that follows, the faculty discuss how they would approach treatment sequencing in later lines of therapy, whether it is necessary to test for BTK inhibitor resistance, how their treatment recommendations might change if the patient’s cytogenetic profile evolved, and more.
This is Part 1 of Treatment Approaches to Relapsed/Refractory CLL: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. To set the stage, Drs. Nicole Lamanna, John Allan, and Inhye Ahn discuss front-line treatment strategies for chronic lymphocytic leukemia (CLL). The patient is a 71-year-old man who presented in 2020 with symptomatic CLL after he was monitored for a period of 4 years. He developed progressive fatigue, weight loss, splenomegaly, and bulky lymphadenopathy. He has a good performance status and adequate renal function. He has a white blood cell count of 113 x 109/L, hemoglobin of 10.3 g/dL, and a platelet count of 105,000/µL. Sequencing reveals deletion 13q, trisomy 12, unmutated IGHV, and TP53 wild-type. In the conversation that follows, the faculty discuss the patient’s prognosis, how comorbidities impact treatment options, time-limited vs continuous therapy, and more.
This is Part 3 of Evolving Treatment Landscape of Indolent Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Laurie Sehn, Gilles Salles, and Sonali Smith discuss the treatment of relapsed/refractory nodal marginal zone lymphoma. The patient is a 68-year-old man who was diagnosed with marginal zone lymphoma in 2019 after a PET/CT scan found a large pelvic mass involving the bladder and causing left-sided hydronephrosis; SUVmax was 7, and LDH was normal. He received bendamustine plus rituximab for six cycles, achieving a complete response on PET. In 2023, surveillance CT showed a recurrent pelvic mass and several mesenteric lymph nodes; PET/CT showed no additional disease, and the SUVmax was 6. In the conversation that follows, the faculty discuss whether transformation is a concern in marginal zone lymphoma, the role of BTK inhibitors, and whether CAR T-cell therapy could be an option for this patient.
This is Part 2 of Evolving Treatment Landscape of Indolent Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Laurie Sehn, Gilles Salles, and Sonali Smith discuss the third-line treatment of relapsed/refractory follicular lymphoma. The patient is a 74-year-old woman who originally presented in 2014 with asymptomatic low-bulk stage IVA follicular lymphoma, grade 1 to 2, for which she received four cycles of rituximab. In 2019, she developed symptomatic disease, with multiple nodes > 7 cm, and received bendamustine plus rituximab for six cycles, achieving a complete response. In December 2024, she presents with fatigue, progressive lymphadenopathy above and below the diaphragm, no B-symptoms, normal LDH, and SUVmax of 10. In the conversation that follows, the faculty discuss next steps for this patient, whether there are any actionable biomarkers for follicular lymphoma, and patient-specific factors to consider when selecting treatment in the third-line setting.
This is Part 1 of Evolving Treatment Landscape of Indolent Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Laurie Sehn, Gilles Salles, and Sonali Smith discuss the second-line treatment of early relapsing follicular lymphoma. The patient is a 41-year-old man originally diagnosed with grade 1 to 2 follicular lymphoma in 2023. He received bendamustine plus rituximab for six cycles, achieving a complete response on PET, and then started rituximab maintenance. After four cycles, he developed shortness of breath on exertion and night sweats. PET/CT confirmed recurrence of lymphadenopathy above and below the diaphragm, as well as a pleural-based mass (SUVmax of 16), pleural effusion, and peritoneal deposits; his LDH was normal. In the conversation that follows, the faculty discuss the clinical implications of progression-of-disease within 24 months in follicular lymphoma, the importance of ruling out transformation, and the role of novel therapies at disease relapse.
Timothy S. Fenske, MD, of the Medical College of Wisconsin presented an initial report from the ECOG-ACRIN EA4151 phase III randomized trial exploring outcomes of autologous hematopoietic cell transplantation (ASCT) in mantle cell lymphoma. The researchers randomized patients in first complete remission with undetectable minimal residual disease and found that ASCT was not associated with improved outcomes (Abstract LBA-6).
Maayan Levy, PhD, and Marco Ruella, MD, of the University of Pennsylvania, Perelman School of Medicine, discuss findings on whether ketogenic diet-derived BHB can be provided as a dietary intervention to augment CAR-T function in multiple cancer models. The results of this study will be translated into a first-in-human clinical trial of BHB-supplementation during CAR-T 19 treatment for relapsed or refractory B cell lymphoma. The data were presented during the ASH Plenary Scientific Session (Abstract 4).
Yasmin H. Karimi, MD, of the University of Michigan Comprehensive Cancer Center, discusses 2.5-year follow-up data on epcoritamab monotherapy for patients with relapsed or refractory large B-cell lymphoma. The subcutaneous regimen continues to demonstrate durable responses (Abstract 7039).
Yasmin H. Karimi, MD, of the University of Michigan Comprehensive Cancer Center, discusses data reaffirming the efficacy and feasibility of using epcoritamab plus R-DHAX/C (rituximab, dexamethasone, cytarabine, and oxaliplatin or carboplatin) in autologous stem cell transplant–eligible patients with diffuse large B-cell lymphoma. Response rates were reported to be high, and most patients proceeded to transplant (Abstract 7032).
William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses up to 5.5 years of follow-up data from the phase II CAPTIVATE study, showing that in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), fixed duration ibrutinib plus venetoclax continues to provide clinically meaningful progression-free disease in those with high-risk genomic features as well as in the overall population (Abstract 7009).
Joshua D. Brody, MD, of the Icahn School of Medicine at Mount Sinai, discusses results from the EPCORE NHL-2 study, which was designed to evaluate the safety and efficacy of epcoritamab-bysp plus rituximab and lenalidomide in the first-line setting for patients with follicular lymphoma and to assess epcoritamab as maintenance therapy in this population (Abstract 7014).
Peter Riedell, MD, of The University of Chicago, discusses phase III findings on the regimen of brentuximab vedotin in combination with lenalidomide and rituximab for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). This therapy demonstrated a survival advantage in the third-line setting, but as this is an interim analysis, questions remain regarding long-term safety and duration of response, according to Dr. Riedell (Abstract LBA7005).
Peter Riedell, MD, of The University of Chicago, discusses phase III results on the use of tucidinostat plus R-CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) with double expression of MYC and BCL2. The regimen appeared to improve event-free survival and complete response rates vs R-CHOP in the front-line setting. As this is an interim analysis, longer-term follow-up will be needed to better understand its impact, says Dr. Riedell.
David J. Andorsky, MD, of the Sarah Cannon Research Institute and Rocky Mountain Cancer Centers, discusses EPCORE NHL-6, an ongoing study of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). As outpatients, the study participants were given subcutaneous epcoritamab-bysp to see whether they could be safely monitored and cytokine-release syndrome appropriately managed in the outpatient setting (Abstract 7029).
Muhit Özcan, MD, of Turkey’s Ankara University School of Medicine, discusses the ongoing phase III BELLWAVE-010 study of nemtabrutinib plus venetoclax vs venetoclax plus rituximab in previously treated patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (Abstract TPS7089).
This is Part 3 of Treatment Strategies for Transplant-Ineligible Relapsed/Refractory DLBCL, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Jason Westin, Dai Chihara, and Caron A. Jacobson discuss the third-line treatment of patients with transplant-ineligible diffuse large B-cell lymphoma (DLBCL). The patient is an 81-year-old man who was initially diagnosed with DLBCL, non-GCB subtype, with an International Prognostic Index Score of 3. He had a 7 x 6 cm retroperitoneal mass causing hydronephrosis and numerous smaller enlarged lymph nodes. He received 6 cycles of R-miniCHOP, and end-of-treatment PET/CT showed a complete response. Six months after completing treatment, a surveillance scan detected suspicion of relapse with multiple enlarged lymph nodes, and a repeat biopsy confirmed DLBCL. He declined a consultation with a CAR T-cell therapy center and was treated with 2 cycles of R-GemOx. Unfortunately, although PET/CT scans confirm that some areas have improved, there are now newly enlarged lymph nodes consistent with progressive disease. In the conversation that follows, the faculty discuss treatment options for patients with transplant-ineligible relapsed/refractory DLBCL, logistical barriers around the use of bispecific antibodies, managing toxicities such as cytokine-release syndrome, and the curative potential for bispecific antibodies.
This is Part 2 of Treatment Strategies for Transplant-Ineligible Relapsed/Refractory DLBCL, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Jason Westin, Dai Chihara, and Caron A. Jacobson discuss the treatment of late relapsing diffuse large B-cell lymphoma (DLBCL). The patient is a 77-year-old woman who was previously diagnosed with DLBCL, GCB subtype, without MYC translocation, and with an International Prognostic Index Score of 2 at diagnosis with stage II disease. She was treated with R-CHOP for 6 cycles; however, she was hospitalized after cycle 4 with neutropenic fever, and cycles 5 and 6 were subsequently dose reduced. She achieved a complete response on the end-of-treatment PET/CT and regained her functional status back to baseline over the next 6 months. Two and half years after treatment, she presents with a new fullness in her right axilla, and a PET/CT shows FDG-avid adenopathy in bilateral axillae and the retroperitoneum. A repeat biopsy confirms DLBCL. In the conversation that follows, the faculty discuss the current standard-of-care treatment options for older patients with DLBCL whose disease progresses after 12 months, whether CAR T-cell therapy would be an option, the importance of repeat biopsy, and the role of tafasitamab plus lenalidomide in patients with DLBCL that is not refractory to initial therapy.
This is Part 1 of Treatment Strategies for Transplant-Ineligible Relapsed/Refractory DLBCL, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Jason Westin, Dai Chihara, and Caron A. Jacobson discuss the treatment of early relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The patient is a 76-year-old man who was diagnosed with DLBCL, non-GCB subtype, with no translocation of MYC and an International Prognostic Index score of 4 at diagnosis. He was treated with 6 cycles of R-CHOP and achieved a complete response on interim PET, but has progressive disease on end-of-treatment PET. He tolerated treatment relatively well and has a performance status of 1. A biopsy confirms refractory DLBCL. He has adequate organ function based on labs, a repeat echocardiogram, and pulmonary function testing, and his health-care team tells him that he is “too old for stem cell transplant.” In the conversation that follows, the faculty discuss the current standard-of-care treatment options for patients with DLBCL that progresses within 12 months of front-line therapy, whether there is a maximum age limit for CAR T-cell therapy, and special considerations that should be taken for patients after treatment with CAR T-cell therapy.
This is Part 3 of Treatment Options for Relapsed/Refractory Follicular Lymphoma: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Andrew M. Evens, L. Elizabeth Budde, and Carla Casulo discuss the third-line treatment of relapsed/refractory follicular lymphoma in a patient with high-risk features. The patient is a 65-year-old Black man who was initially diagnosed in 2014 and treated with R-CHOP followed by 2 years of rituximab maintenance. After his disease progressed in 2020, he was treated with bendamustine/obinutuzumab, obtaining a complete response, and then received obinutuzumab maintenance until April 2022. In February 2023, he presented with increasing abdominal pressure, fatigue, and drenching night sweats. A PET scan revealed multifocal disease progression, including a bulky left lower quadrant soft tissue mass near the lumbar spine. A biopsy confirmed grade 3 follicular lymphoma with prominent necrosis and multiple patches of large cells; it was positive for CD20, CD10, BCL-2, and BCL-6, and the Ki-67 was 60% to 70%. In the conversation that follows, the faculty discuss treatment options for patients with high-risk features, choosing between CAR T-cell–based therapies and bispecific antibodies in the third-line setting, and important considerations when administering CD3/CD20-targeted bispecific antibodies in the community setting.
This is Part 2 of Treatment Options for Relapsed/Refractory Follicular Lymphoma: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Andrew M. Evens, L. Elizabeth Budde, and Carla Casulo discuss the management of patients with follicular lymphoma who experience progression of disease within 24 months (POD-24). The patient is a 71-year-old fit, White man who presented with fatigue and diffuse lymphadenopathy. After undergoing an excisional node biopsy, he was found to have follicular lymphoma grade 1/2 out of 3. A staging PET scan showed multiple hypermetabolic lesions. He received bendamustine/rituximab induction therapy for 6 cycles and obtained a metabolic complete response; he did not receive rituximab maintenance. Eight months later, he presented with swelling of the right eyelid with new, painful soft tissue lesions. A PET scan showed multiple hypermetabolic subcutaneous nodules in the upper back, left inguinal and right inguinal nodes, and right lateral thigh. In the conversation that follows, the faculty discuss the meaning and clinical implication of POD-24, optimal treatment options for patients who experience early recurrence, and whether autologous stem cell transplant is still an option in 2024.
This is Part 1 of Treatment Options for Relapsed/Refractory Follicular Lymphoma: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Andrew M. Evens, L. Elizabeth Budde, and Carla Casulo discuss the second-line treatment of relapsed follicular lymphoma in a patient with comorbidities. The patient is a 74-year-old Asian man who was diagnosed 5 years ago with follicular lymphoma grade 1/2 out of 3 and a Ki-67 score of 5% to 10%. His ECOG performance status was 1, but he had multiple comorbidities that led to a CIRS-G score of 12. After achieving a metabolic complete response on single-agent rituximab therapy, he received 2 years of rituximab maintenance therapy. Remission was maintained for 4 years, but 18 months after his last rituximab, he presented with right leg swelling that was negative for deep vein thrombosis. A coronal PET/CT scan showed a new large retroperitoneal mass abutting the right psoas and iliopsoas muscles, encasing his iliac vessels and ureter. In the conversation that follows, the faculty discuss the importance of repeat biopsy and molecular testing in patients with relapsed follicular lymphoma, how past medical history and comorbidities influence treatment choice, and the clinical implications of the AUGMENT trial.
Mazyar Shadman, MD, MPH, of the University of Washington, discusses new data suggesting that in patients with relapsed large B-cell lymphoma who achieve a complete response, treatment with autologous transplantation may be associated with a lower relapse rate and improved progression-free survival compared with CAR T-cell therapy, including those with early treatment failure (Abstract 781).
Sanjal H. Desai, MBBS, of the University of Minnesota, discusses results from a multicenter cohort, which shows that, for transplant-eligible patients with relapsed or refractory classical Hodgkin lymphoma, PD-1–based salvage therapy at any point before transplantation is associated with improved progression-free survival, compared with brentuximab vedotin or chemotherapy-based salvage regimens (Abstract 182).
Adam S. Kittai, MD, of The Ohio State University, discusses his data supporting the use of CAR T-cell therapy for patients with Richter’s transformation. Given the high response rate to CD19 CAR T-cell treatment, along with early relapse in most patients, allogeneic stem cell transplantation at response should also be considered, he says (Abstract 108).
Michael Wang, MD, of The University of Texas MD Anderson Cancer Center, discusses phase III results from the Sympatico study, which shows the combination of ibrutinib and venetoclax improved progression-free survival vs ibrutinib plus placebo in patients with relapsed or refractory mantle cell lymphoma. According to Dr. Wang, these findings demonstrate a favorable benefit-risk profile for ibrutinib plus venetoclax in this patient population (Abstract LBA2).
Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center, discusses phase I/II findings of the BRUIN study on the use of pirtobrutinib after covalent Bruton’s tyrosine kinase (BTK) inhibitors in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). The results suggest that continuing BTK pathway inhibition following a covalent BTK inhibitor may be an important sequencing approach to consider in the treatment of CLL/SLL (Abstract 325).
Sarah C. Rutherford, MD, of Weill Cornell Medicine, discusses findings of the SWOG S1826 study, which showed nivolumab plus AVD (doxorubicin, vinblastine, and dacarbazine) improved progression-free and event-free survival and seemed to be better tolerated than brentuximab vedotin plus AVD in patients aged 60 and older with advanced-stage Hodgkin lymphoma (Abstract 181).
William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from the phase I/II BRUIN study, which shows encouraging response and overall survival in patients with Richter transformation. Although this condition remains a challenging diagnosis, pirtobrutinib represents a potential treatment option that warrants further investigation, according to Dr. Wierda (Abstract 1737).
Mikkael A. Sekeres, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, reviews key abstracts from ASH 2023 on treatment of myelofibrosis, chronic lymphocytic leukemia, large B-cell lymphoma, and acute myeloid leukemia (Abstracts 620, 631, 781, 425).
Bijal D. Shah, MD, of Moffitt Cancer Center and Research Institute, discusses a matching-adjusted indirect comparison of brexucabtagene autoleucel and pirtobrutinib in patients with relapsed or refractory mantle cell lymphoma who have been previously treated with a BTK inhibitor (Abstract 5136).
Jonathon B. Cohen, MD, of Winship Cancer Institute, Emory University, discusses safety and efficacy findings from the phase I/II BRUIN study. The trial found that pirtobrutinib continues to demonstrate durable efficacy and a favorable safety profile in heavily pretreated patients with relapsed or refractory mantle cell lymphoma (Abstract 981).
Matthew J. Frank, MD, PhD, of Stanford University School of Medicine, discusses new findings showing that CD22 chimeric antigen receptor (CAR) T-cell therapy is an effective and safe salvage therapy for patients with CAR19-refractory large B-cell lymphoma. A multicenter phase II clinical trial is planned for 2023 (Abstract S230).
This is Part 3 of Clinical Advances in Diffuse Large B-Cell Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Jeremy Abramson, Laurie Sehn, and Kieron Dunleavy discuss the third-line treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Their patient was most recently treated with axicabtagene ciloleucel as second-line treatment for DLBCL, non–germinal center subtype, which had originally relapsed 11 months after treatment with pola-R-CHP. She develops grade 2 cytokine-release syndrome on day 2 of treatment with axicabtagene ciloleucel, but her symptoms resolve rapidly upon receiving tocilizumab. She develops confusion on day 4, consistent with grade 2 ICANS, for which she receives dexamethasone with improvement over 7 days. She has a very good partial response at 30 days, but at day 60 her disease progresses again. As they consider the next steps for this patient, the faculty discuss the importance of tailoring treatment to the patient’s needs and goals when therapy is unlikely to be curative. They review current novel therapies that have entered the treatment landscape, including combinations such as polatuzumab plus bendamustine/rituximab, as well as the recently approved bispecific antibodies glofitamab and epcoritamab.
This is Part 2 of Clinical Advances in Diffuse Large B-Cell Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Jeremy Abramson, Laurie Sehn, and Kieron Dunleavy discuss the second-line treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Their patient is now 73 years of age and originally received pola-R-CHP for her DLBCL. Eleven months after completing treatment, she experiences biopsy-proven relapse involving nodes above and below the diaphragm and multifocal bone involvement. The faculty review their next steps in the second-line setting. They discuss considerations when selecting among CAR T-cell products, the logistics of CAR T-cell therapy and approaches to bridging therapy, as well as options for second-line therapy for patients who are not eligible for CAR T-cell therapy.
This is Part 1 of Clinical Advances in Diffuse Large B-Cell Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Jeremy Abramson, Laurie Sehn, and Kieron Dunleavy discuss the treatment of newly diagnosed high-risk diffuse large B-cell lymphoma (DLBCL). The patient is a 72-year-old woman who presents with adenopathy, fevers, and drenching night sweats. An axillary lymph node biopsy reveals DLBCL, non–germinal center B-cell subtype, without translocations of MYC or BCL2, but with IHC expression. Positron-emission tomography/computed tomography shows stage IV disease with liver and kidney involvement. Her LDH is elevated, ECOG performance status is 1, and International Prognostic Index is 4. In the conversation that follows, the faculty discuss their recommended chemotherapy regimen for patients such as this, whether there are patient- or disease-specific factors to consider when selecting between R-CHOP and Pola-R-CHP, and the role of CNS prophylaxis.
This is Part 3 of Clinical Advances in Mantle Cell Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Brad Kahl, Jonathon Cohen, and Peter Martin discuss the second-line treatment of relapsed/refractory mantle cell lymphoma. The patient is a 76-year-old man with a history of mantle cell lymphoma who received bendamustine/rituximab followed by rituximab maintenance 5 years prior for advanced-stage disease. His recurrence was detected recently by physical exam with new axillary and cervical adenopathy; he has normal blood counts, and there is no bone marrow involvement. PET scan imaging shows several sites of nodal involvement plus splenic involvement, his performance status is 0, and he has no major comorbidities. The faculty discuss next steps for this patient, including the importance of repeat biopsies for patients with relapsed/refractory disease. They review major treatment options in the second line, particularly the role of BTK inhibitors and CAR T-cell therapy.
This is Part 2 of Clinical Advances in Mantle Cell Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Brad Kahl, Jonathon Cohen, and Peter Martin discuss the management of newly diagnosed mantle cell lymphoma in older patients. The patient is a 74-year-old man who presents to the clinic for the evaluation of worsening back pain. Computed tomography shows bulky retroperitoneal and mesenteric adenopathy, which leads to a biopsy that revealed mantle cell lymphoma (cyclin D1 positive) with a Ki-67 of 15%. He has extensive disease on PET imaging, with 20% marrow involvement and a high-intermediate MIPI-C score. The faculty discuss what their initial treatment considerations would be for this patient, and how a p53 mutation might change their strategy. They also discuss a recent real-world analysis showing the benefit of maintenance rituximab after both R-CHOP and bendamustine/rituximab, as well as the SHINE study of ibrutinib added to standard therapy in newly diagnosed older patients with mantle cell lymphoma.
This is Part 1 of Clinical Advances in Mantle Cell Lymphoma, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Brad Kahl, Jonathon Cohen, and Peter Martin discuss the management of newly diagnosed mantle cell lymphoma in younger patients. The patient is a 54-year-old man who presents with inguinal lymphadenopathy and increasing fatigue. He has widespread adenopathy in the 3-4 cm range, and the spleen tip is palpable. Lymph node biopsy shows classic mantle cell lymphoma with Ki-67 of 35%; PET imaging shows involvement of most nodal regions with some bladder compression; and bone marrow biopsy shows 40% mantle cell lymphoma involvement, but no 17p deletion of p53 mutation. The patient is classified as low-intermediate risk on MIPI-C. The faculty discuss the next steps for this patient in light of the changing treatment landscape for mantle cell lymphoma in younger individuals. They consider whether a watch-and-wait approach might be appropriate, the role of novel agents in induction regimens, and treatment de-intensification strategies.
Reid Merryman, MD, of Dana-Farber Cancer Institute, discusses his findings on the regimen of epcoritamab plus rituximab and lenalidomide for patients with high-risk follicular lymphoma. Regardless of whether their disease progressed within 24 months of first-line chemoimmunotherapy, this regimen showed antitumor activity and a manageable safety profile in patients with relapsed or refractory disease. Epcoritamab, a subcutaneous T-cell–engaging bispecific antibody, may abrogate the negative effects of high-risk features (Abstract 7506).
Tycel J. Phillips, MD, of City of Hope National Medical Center, and Emanuele Zucca, MD, of the Oncology Institute of Southern Switzerland and the International Extranodal Lymphoma Study Group, discuss findings from the largest prospective study of patients with primary mediastinal B-cell lymphoma. The trial data support omitting radiotherapy in patients who achieve complete metabolic response after immunochemotherapy (Abstract LBA7505).
Jennifer L. Crombie, MD, of Dana-Farber Cancer Institute, discusses the historically poor outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Her study examined real-world data on the use of novel therapies in this population and found that outcomes with second- and third-line regimens of polatuzumab vedotin-piiq plus bendamustine and rituximab and tafasitamab plus lenalidomide remain suboptimal, with worse outcomes particularly after chimeric antigen receptor T-cell therapy (Abstract 7552).
Nirav N. Shah, MD, of the Medical College of Wisconsin, discusses the efficacy and safety of pirtobrutinib, a highly selective, noncovalent BTK inhibitor, studied for more than 3 years in the BRUIN trial. The results showed that the use of pirtobrutinib continues to have durable efficacy and a favorable safety profile in heavily pretreated patients with relapsed or refractory mantle cell lymphoma and prior BTK inhibitor therapy. Responses were observed in patients with high-risk disease features, including blastoid/pleomorphic variants, elevated Ki67 index, and TP53 mutations (Abstract 7514).
Nirav N. Shah, MD, of the Medical College of Wisconsin, discusses the efficacy and safety of pirtobrutinib, a highly selective, noncovalent BTK inhibitor, studied for more than 3 years in the BRUIN trial. The results showed that the use of pirtobrutinib continues to have durable efficacy and a favorable safety profile in heavily pretreated patients with relapsed or refractory mantle cell lymphoma and prior BTK inhibitor therapy. Responses were observed in patients with high-risk disease features, including blastoid/pleomorphic variants, elevated Ki67 index, and TP53 mutations (Abstract 7514).
Nirav N. Shah, MD, of the Medical College of Wisconsin, discusses phase II results showing that split-dose R-CHOP offers older patients with diffuse large B-cell lymphoma (DLBCL) an equivalent dose intensity as R-CHOP-21 through a fractionated dosing schedule, improving tolerability. At the end of treatment for these older patients, a complete response rate of 71% was comparable to outcomes with R-CHOP in younger patients with the disease (Abstract 7554).
Catherine C. Coombs, MD, of the University of California, Irvine, discusses prolonged pirtobrutinib therapy, which continues to demonstrate a safety profile amenable to long-term administration at the recommended dose without evidence of new or worsening toxicity signals. The safety and tolerability observed in patients on therapy for 12 months or more were similar to previously published safety analyses of all patients enrolled, regardless of follow-up (Abstract 7513).
Tycel J. Phillips, MD, and Swetha Kambhampati, MD, both of City of Hope National Medical Center, discuss new findings showing that the real-world effectiveness and safety of brexucabtagene autoleucel were similar to data from the pivotal ZUMA-2 trial in patients with relapsed or refractory mantle cell lymphoma, regardless of prior BTK inhibition, bendamustine, or autologous stem cell transplantation (Abstract 7507).
Manali K. Kamdar, MD, of University of Colorado Hospital, discusses the treatment landscape for the 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) whose disease will relapse. Patients who experience relapse within 1 year of chemoimmunotherapy have poor outcomes with autotransplantation, but chimeric antigen receptor T-cell therapy has shown efficacy and manageable toxicity.
Tycel J. Phillips, MD, and Alex F. Herrera, MD, both of the City of Hope National Medical Center, discuss results from the SWOG S1826 study, which showed that nivolumab and AVD (doxorubicin, vinblastine, and dacarbazine) improved progression-free survival vs brentuximab vedotin plus AVD in patients with advanced-stage classical Hodgkin lymphoma. Longer follow-up is needed to assess overall survival and patient-reported outcomes. This trial may be a key step toward harmonizing the pediatric and adult treatment of advanced-stage disease (LBA4).
Tycel J. Phillips, MD, and Alex F. Herrera, MD, both of the City of Hope National Medical Center, discuss findings from the POLARIX study, which provided the largest prospectively collected circulating tumor DNA (ctDNA) data set on patients with previously untreated diffuse large B-cell lymphoma. Achieving ctDNA-negative status was associated with improved outcomes when patients were treated with polatuzumab vedotin-piiq plus combination chemotherapy vs combination chemotherapy alone (Abstract 7523).