Optimizing the Current and Future Management of Relapsed/Refractory Diffuse Large B-Cell Lymphoma — Video Program

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of diffuse large B-cell lymphoma.

LEARNING OBJECTIVES

• Apply available clinical research findings in the formation of evidence-based therapeutic approaches for patients with relapsed/refractory (R/R) DLBCL both fit and unfit for intensive therapy.
• Evaluate the mechanisms of action of and available clinical trial findings with various CD19-directed therapies approved for R/R DLBCL, and assess the spectrum and frequency of associated toxicities.
• Appraise the biological rationale for, recently presented research findings with and the potential clinical role of CD30-targeted antibody-drug conjugate-based therapy for R/R DLBCL.
• Consider published research data with and the current clinical role of CD20 x CD3 bispecific antibodies for R/R DLBCL.
• Identify patients with R/R DLBCL for whom treatment with chimeric antigen receptor T-cell therapy would be appropriate.
• Counsel appropriate patients regarding the potential benefits of participation in ongoing clinical studies evaluating novel agents and strategies for R/R DLBCL.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Interview: Research To Practice designates this enduring material for a maximum of 2.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and a short post-test, enables the participant to earn up to 2.75 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialties: medical oncology and hematology.

PRIVACY POLICY
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HOW TO USE THIS CME ACTIVITY
Video Program: This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/DLBCLThinkTank2024/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Martin Hutchings, MD, PhD
Senior Consultant
Department of Haematology and Phase 1 Unit
Rigshospitalet, Copenhagen University Hospital
Professor of Clinical Lymphoma Research
Department of Clinical Medicine, University of Copenhagen
Copenhagen, Denmark

Advisory Committees and Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Genmab US Inc, Janssen Biotech Inc, Merck, Roche Laboratories Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Celgene Corporation, Genentech, a member of the Roche Group, Genmab US Inc, Incyte Corporation, Janssen Biotech Inc, Johnson & Johnson Pharmaceuticals, Merck, Novartis, Pfizer Inc, Roche Laboratories Inc, Takeda Pharmaceuticals USA Inc; Data and Safety Monitoring Boards/Committees: Genmab US Inc, Roche Laboratories Inc.

Manali Kamdar, MD, MBBS
Associate Professor
Clinical Director of Lymphoma Services
Morton and Sandra Saffer Endowed Chair in Hematology Research
Division of Hematology, Hematologic Malignancies
University of Colorado Cancer Center
Aurora, Colorado

Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeiGene Ltd, Bristol Myers Squibb, Celgene Corporation, Genentech, a member of the Roche Group; Contracted Research: Novartis; Data and Safety Monitoring Boards/Committees: Celgene Corporation, Genentech, a member of the Roche Group.

Matthew Lunning, DO
Associate Professor of Medicine
Medical Director, Cellular Therapy
Associate Vice Chair of Research
Assistant Vice Chancellor for Clinical Research
Division of Hematology/Oncology
Department of Internal Medicine
University of Nebraska Medical Center
Omaha, Nebraska

Consulting/Honoraria: AbbVie Inc, Acrotech Biopharma, ADC Therapeutics, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Caribou Biosciences Inc, Fate Therapeutics, Genentech, a member of the Roche Group, Genmab US Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, Kite, A Gilead Company, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Nurix Therapeutics Inc, Pfizer Inc, Recordati, Regeneron Pharmaceuticals Inc, Seagen Inc, Veeva, Vittoria Biotherapeutics; Research Funding: AbbVie Inc,Bristol Myers Squibb, Fate Therapeutics, Kite, A Gilead Company.

Gilles Salles, MD, PhD
Service Chief, Lymphoma Service
Steven Greenberg Chair
Memorial Sloan Kettering Cancer Center
Weill Cornell Medical College
New York, New York

Advisory Committees: AbbVie Inc, BeiGene Ltd, Bristol Myers Squibb, Genentech, a member of the Roche Group, Genmab US Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, Kite, A Gilead Company, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Novartis, Nurix Therapeutics Inc, Pfizer Inc; Consulting Agreements: AbbVie Inc, ATB Therapeutics, BeiGene Ltd, Bristol Myers Squibb, Debiopharm, Genentech, a member of the Roche Group, Genmab US Inc, Incyte Corporation, Innate Pharma, Ipsen Biopharmaceuticals Inc, Kite, A Gilead Company, ModeX Therapeutics, Molecular Partners, Orna Therapeutics, Treeline Biosciences; Contracted Research: AbbVie Inc, Genentech, a member of the Roche Group, Genmab US Inc, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, Nurix Therapeutics Inc.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: AbbVie Inc, ADC Therapeutics, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeiGene Ltd, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Clovis Oncology, Coherus BioSciences, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Hologic Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Jazz Pharmaceuticals Inc, Karyopharm Therapeutics, Kite, A Gilead Company, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from ADC Therapeutics, Genentech, a member of the Roche Group, and Incyte Corporation.

Release date: February 2025
Expiration date: February 2026

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Kamdar

Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of the phase 3 TRANSFORM study. Blood 2023;141(14):1675-84. Abstract

Abramson JS et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet 2020;396(10254):839-52. Abstract

Bishop MR et al. Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma. N Engl J Med 2022;386(7):629-39. Abstract

Cordeiro A et al. Late events after treatment with CD19-targeted chimeric antigen receptor modified T cells. Biol Blood Marrow Transplant 2020;26(1):26-33. Abstract

Crump M et al. Outcomes in refractory diffuse large B-cell lymphoma: Results from the international SCHOLAR-1 study. Blood 2017;130(16):1800-8. Abstract

Gisselbrecht C et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 2010;28(27):4184-90. Abstract

Hill HA et al. Genetic mutations and features of mantle cell lymphoma: A systematic review and meta-analysis. Blood Adv 2020;4(13):2927-38. Abstract

Hines MR et al. Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Transplant Cell Ther 2023;29(7):438.e1-16. Abstract

Jacobson CA. CD19 chimeric antigen receptor therapy for refractory aggressive B-cell lymphoma. J Clin Oncol 2019;37(4):328-35. Abstract

Kamdar M et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet 2022;399(10343):2294-308. Abstract

Kramer AM et al. CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: Continued durable remissions at 3-year follow-up. ASH 2024;Abstract 69.

Lee DW et al.ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells.Biol Blood Marrow Transplant 2019;25(4):625-38. Abstract

Locke FL et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med 2022;386(7):640-54. Abstract

Locke FL et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): A single-arm, multicentre, phase 1-2 trial. Lancet Oncol 2019;20(1):31-42. Abstract

Morris EC et al. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol 2022;22(2):85-96. Abstract

Rejeski K et al. CAR-HEMATOTOX: A model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood 2021;138(24):2499-513. Abstract

Riedell PA et al. Rapcabtagene autoleucel (YTB323) in patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL): Phase II trial clinical update. ASH 2024;Abstract 67.

Schuster SJ et al. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): A multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 2021;22(10):1403-15. Abstract

Sehgal A et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): An open-label, phase 2 study. Lancet Oncol 2022;23(8):1066-77. Abstract

 

Prof Hutchings

Abramson J et al. Glofitamab plus gemcitabine and oxaliplatin (GLOFIT-GEMOX) for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Results of a global randomized phase III trial (STARGLO). EHA 2024;Abstract LB3438.

Abramson JS et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet 2020;396(10254):839-52. Abstract

Bannerji R et al. Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): Results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Haematol 2022;9(5):e327-39. Abstract

Budde LE et al. Single-agent mosunetuzumab shows durable complete responses in patients with relapsed or refractory B-cell lymphomas: Phase I dose-escalation study. J Clin Oncol 2022;40(5):481-91. Abstract

Crochet G et al. Efficacy of CAR T-cell therapy is not impaired by previous bispecific antibody treatment in large B-cell lymphoma. Blood 2024;144(3):334-8. Abstract

Dickinson MJ et al. Fixed-duration glofitamab monotherapy continues to demonstrate durable responses in patients with relapsed or refractory large B-cell lymphoma: 3-year follow-up from a pivotal phase II study. ASH 2024;Abstract 865.

Dickinson MJ et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 2022;387(24):2220-31. Abstract

Dickinson MJ et al. Glofitamab induces durable complete remissions and has favorable safety in patients with relapsed/refractory diffuse large B-cell lymphoma and ≥2 prior therapies: Pivotal phase II expansion results. EHA 2022;Abstract S220.

Hiemstra IH et al. Potent anti-tumor activity of DuoBody^®-CD3xCD20 in preclinical models in vitro and in vivo. EHA 2019;Abstract PS1301.

Hutchings M et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: An open-label, phase 1/2 study. Lancet 2021;398(10306):1157-69. Abstract

Hutchings M et al. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: A phase I trial. J Clin Oncol 2021;39(18):1959-70. Abstract

Lussana F et al. Immunotherapy of acute lymphoblastic leukemia and lymphoma with T cell-redirected bispecific antibodies. J Clin Oncol 2021;39(5):444-55. Abstract

Thieblemont C et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: Dose expansion in a phase I/II trial. J Clin Oncol 2023;41(12):2238-47. Abstract

Vose JM et al. 3-year update from the Epcore NHL-1 trial: Epcoritamab leads to deep and durable responses in relapsed or refractory large B-cell lymphoma. ASH 2024;Abstract 4480.

 

Prof Salles

Caimi PF et al. Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: Long-term efficacy and safety from the phase II LOTIS-2 study. Haematologica 2024;109(4):1184-93. Abstract

Caimi PF et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): A multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2021;22(6):790-800. Abstract

Cheson BD et al. Diffuse large B-cell lymphoma: New targets and novel therapies. Blood Cancer J 2021;11(4):68. Abstract

Crombie JL et al. Real-world outcomes with novel therapies in R/R DLBCL. ASCO 2023;Abstract 7552.

Duell J et al. Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: Final 5-year efficacy and safety findings in the phase II L-MIND study. Haematologica 2024;109(2):553-66. Abstract

Duell J et al. Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Haematologica 2021;106(9):2417-26. Abstract

Kim C et al. Real-world outcomes of polatuzumab vedotin with bendamustine and rituximab as salvage and bridge therapy to CAR T-cell treatment in relapsed/refractory diffuse large B-cell lymphoma. ASH 2024;Abstract 3107.

Paillassa J et al. Tafasitamab lenalidomide in relapsed/refractory large B-cell lymphomas: A multicentric real-world French experience study. Hematological Oncology 2023;41:591-2. Abstract

Qualls DA et al. Tafasitamab and lenalidomide in large B-cell lymphoma: Real-world outcomes in a multicenter retrospective study. Blood 2023;142(26):2327-31. Abstract

Salles G et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): A multicentre, prospective, single-arm, phase 2 study. Lancet Oncol 2020;21(7):978-88. Abstract

Saverno K et al. Real-world effectiveness of tafasitamab (tafa) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in the United States. ASH 2024;Abstract 2375.

Sehn LH et al. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: Survival update and new extension cohort data. Blood Adv 2022;6(2):533-43. Abstract

Sehn LH et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 2020;38(2):155-65. Abstract

Sehn LH, Salles G. Diffuse large B-cell lymphoma. N Engl J Med 2021;384(9):842-58. Abstract

 

Dr Lunning

Bartlett NL et al. Brentuximab vedotin combination for relapsed diffuse large B-cell lymphoma. J Clin Oncol 2025;[Online ahead of print]. Abstract

Bartlett NL et al. Outcomes in older patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) from the ECHELON-3 study. ASH 2024;Abstract 4483.

Chavez JC et al. Efficacy and safety of golcadomide, a novel cereblon E3 ligase modulator (CELMoD) agent, combined with rituximab in a phase 1/2 open-label study of patients with relapsed/refractory non-Hodgkin lymphoma. ASH 2023;Abstract 4496.

Kim JA et al. Brentuximab vedotin in combination with lenalidomide and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma: Results from the phase 3 ECHELON-3 study. ASCO 2024;Abstract LBA7005.

Matasar M et al. Efficacy and safety of odronextamab monotherapy in patients (pts) with diffuse large B-cell lymphoma (DLBCL) progressing after CAR T-cell therapy: Primary analysis from the ELM-1 study. ASH 2024;Abstract 866.

Michot J-M et al. Longer follow-up of golcadomide (GOLCA), a cereblon E3 ligase modulator (CELMoD™) agent ± rituximab (RTX), in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). ASH 2024;Abstract 869.