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238 Treatment Patterns and Outcomes Following Progression of Disease Post-CAR-T Therapy in Relapsed or Refractory Mantle Cell Lymphoma: A Multicenter Analysis

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Therapies for Mantle Cell Lymphoma
Hematology Disease Topics & Pathways:
Research, Adult, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Diseases, Real-world evidence, Aggressive lymphoma, Treatment Considerations, Lymphoid Malignancies, Study Population, Human
Saturday, December 7, 2024: 2:45 PM

Zachary D. Epstein-Peterson, MD1,2, Anath Lionel, MD, PhD3, Ashlee Joseph, BS1*, Esther Drill, DrPH4*, Suheil Albert Atallah-Yunes, MD5, Taylor R. Brooks, MD6, Elise A. Chong, MD7,8, Emeline R. Chong8*, Jamie Dela Cruz9*, Matthew J. Frank10,11, Andrew Ip, MD, MSc12, Madiha Iqbal, MD13, Caron A. Jacobson, MD, MMSc14, Manali K. Kamdar, MD15, Reem Karmali, MD16,17, Kami J. Maddocks, MD18, Matthew Matasar, MD, MS19, Reid W. Merryman, MD14, Javier Munoz, MD20*, Peter A. Riedell, MD21, Christine E. Ryan, MD14, Gilles Salles, MD, PhD22,23, Craig S. Sauter, MD24, Yazeed Sawalha, MD25, Roni Shouval, MD, PhD26,27, Navika Shukla, MD28, Alexander V. Stanisic, MD29*, Dylan Therwhanger, MD8*, Herman Van Besien, md30, Yucai Wang, MD, PhD31, Samuel Yamshon, MD32*, Andrew D. Zelenetz, MD, PhD1, Maria Lia Palomba, MD1,23, Preetesh Jain, MD, MBBS, PhD, DM33 and Anita Kumar, MD34

1Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
2Department of Medicine, Weill Cornell Medical College, New York, NY
3Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX
4Memorial Sloan Kettering Cancer Center, New York, NY
5Division of hematology, Mayo Clinic, Rochester, MN
6Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
7Department of Medicine, Division of Hematology/Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
8Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
9Dana Farber Cancer Institute, Boston, MA
10Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA
11Stanford Cancer Institute, Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford, CA
12Lymphoma Division, John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ
13Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL
14Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
15University of Colorado, Denver, CO
16Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL
17Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
18The James Cancer Center, The Ohio State University, Columbus, OH
19Division of Blood Disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health, New York, NY
20Mayo Clinic, Phoenix, AZ
21Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
22Lymphoma Service Chief, Memorial Sloan Kettering Cancer Center, New York, NY
23Department of Medicine, Weill Cornell Medical College, New York
24Department of Hematology and Medical Oncology Cleveland Clinic, Cleveland, OH
25Division of Hematology, The Ohio State University, Columbus, OH
26Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
27Department of Medicine, Weill Cornell Medicine, New York, NY
28Department of Medicine, University of Chicago, Chicago, IL
29Northwestern University Feinberg School of Medicine, Chicago, IL
30Weill Cornell Medicine, New York, NY
31Division of Hematology, Mayo Clinic, Rochester, MN
32Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY
33Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
34Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Short Hills, NJ

Background: CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy is an established treatment with high efficacy in treating relapsed or refractory (R/R) mantle cell lymphoma (MCL). However, with CAR-T therapy, refractory disease occurs and a continuous pattern of relapse over time has been observed. Limited data exist about post-CAR-T progression of disease (POD) management and outcomes in MCL. Such data would meaningfully inform practice and set a critical benchmark for future studies in the post-CAR-T setting. We characterized treatment patterns and outcomes for pts with POD after CD19 CAR-T therapy for R/R MCL.

Methods: We queried institutional databases to identify pts with R/R MCL who received CD19-directed CAR-T therapy. Treatment may have occurred as standard-of-care or in a clinical trial. We performed chart review to extract variables and categorized therapies by mechanism(s) of action. We used descriptive statistics to characterize patient/disease characteristics and treatment patterns, the reverse Kaplan-Meier method to calculate follow-up, the Kaplan-Meier method to calculate survival, and Cox proportional hazards to associate clinical and disease features with survival outcomes.

Results: Across 9 sites, we identified 306 pts who received CD19 CAR-T for R/R MCL, of which 104 (34%) experienced POD and were investigated in detail: pts with POD were mostly men (73%), had a median age of 67 yrs (range 36-86) at infusion, and had received a median of 3 lines of therapy pre-leukapheresis, including a BTK inhibitor (BTKi) in 97% of patients; 36% of BTKi-exposed patients had BTKi-unresponsive disease. High-risk tumor features were common pre-CAR-T: 47/68 (69%) with a TP53 mutation, 66/93 (71%) with Ki67 ≥50%, and 47/102 (46%) with blastoid/pleomorphic MCL. Most pts (75%) received bridging therapy. Pts received brexucabtagene autoleucel (88%) or lisocabtagene maraleucel (12%).

Regarding best CAR-T response for pts with POD, 71% had a complete response (CR), 13% partial response (PR), and 15% had no response. The median time from CAR-T infusion to POD was 6 months (IQR 3-12). At time of POD, high-risk MCL features were again common: 55% blastoid/pleomorphic, 42/56 (75%) Ki67 ≥50%, 51/83 (61%) MIPIb high-risk, and 21/35 (60%) TP53-mutated MCL. Among 69 pts with CD19 assessed on a post-POD biopsy, 8 (12%) had CD19-negative disease. 30% of pts had an ECOG performance status of ≥2 at time of POD.

After POD occurred, 15 pts received no anti-lymphoma therapy (Tx), 11 pts underwent excision or radiation, and 78 pts received systemic therapy. The most commonly used first-line systemic Tx post-CAR-T progression included: pirtobrutinib in 13 pts [overall response rate (ORR) 31%], chemoimmunotherapy in 12 pts (ORR 25%), venetoclax in 10 patients (ORR 20%), bispecific antibodies (BsAb) in 10 pts (ORR 60%), and small molecule combinations (at least 2 of BTK inhibitor, BCL2 inhibitor, and lenalidomide) in 8 patients with ORR 50%. The ORR to all first systemic Tx post-POD was 42%.

The median follow-up from POD is 15.2 months among survivors. The median progression-free and overall survival (OS) from time of POD were 2.3 (95% CI 1.9-3.4) and 5.4 months (95% CI 4.5-9.4), respectively, and 1-year OS rate was 33%. TP53 mutations predicted inferior OS (HR 2.83, 95% CI 1.08-7.43, P = 0.026) as did age ≥65 years at time of POD (HR 1.83, 95% CI 1.07-3.15, P = 0.023), MIPIb high-risk (HR 3.56, 95% CI 1.08-11.7, P = 0.042), and non-response to CAR-T (HR 3.55, 95% CI 1.93-6.53, P < 0.001).

Discussion: Our data, the largest reported cohort of pts with POD post-CAR-T with R/R MCL, confirm the poor prognosis in this patient population, with a median OS of 5.4 months. BsAbs showed promise with an overall response rate of 60%. The presence of a TP53 mutation significantly predicted inferior OS, corroborating the prognostic importance of this finding in the post-CAR-T context. Data from pts treated at additional sites and updated analyses will be presented at the meeting.

Disclosures: Epstein-Peterson: Viracta: Research Funding; Genmab: Consultancy; Kymera: Research Funding; OncLive: Honoraria; Amgen: Research Funding. Chong: Nurix: Research Funding; CARGO: Research Funding; Genentech/Roche: Research Funding; AbbVie: Research Funding; AstraZeneca: Consultancy, Research Funding; Beigene: Consultancy; Genmab: Research Funding. Frank: BRVLH: Consultancy; Adaptive Biotechnologies: Consultancy, Research Funding; Cargo Therapeutics: Consultancy, Other: Travel Support; Allogene Therapeutics: Consultancy, Research Funding; Gilead: Consultancy, Other: Travel Support; Roche/Genentech: Current holder of stock options in a privately-held company; EcoR1: Consultancy; Kite-Pharma-Gilead: Consultancy, Research Funding. Iqbal: Sanofi US: Consultancy. Jacobson: Pfizer: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Instil Bio: Consultancy; ADC Therapeutics: Consultancy; Abintus Bio: Consultancy; Bristol Myers Squibb/Celgene: Consultancy; Caribou Biosciences: Consultancy; MorphoSys: Consultancy; Miltenyi: Consultancy; Ipsen: Consultancy; ImmPACT Bio: Consultancy; Synthekine: Consultancy; Novartis: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy. Kamdar: Celgene: Other: Data Monitoring Committee; Beigene: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Genentech: Other: Data Monitoring Committee; Novartis: Research Funding; SeaGen: Speakers Bureau. Karmali: AstraZeneca: Speakers Bureau; Ipsen: Speakers Bureau; Genmab: Honoraria; Genentech/Roche: Honoraria; BeiGene: Speakers Bureau; Incyte: Speakers Bureau; BMS: Honoraria; Abbvie: Honoraria. Maddocks: Genentech: Consultancy; Janssen: Consultancy; Gilead/KITE: Consultancy; Incyte: Consultancy; Lilly: Consultancy; Genmab: Consultancy; BMS: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; AbbVie: Consultancy; MorphoSys: Consultancy. Matasar: IMV Therapeutics: Honoraria; Johnson & Johnson: Consultancy, Honoraria, Research Funding; Merck: Current equity holder in publicly-traded company; Roche: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Allogene: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; GM Biosciences: Consultancy, Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Immunovaccine Technologies: Research Funding; Kite: Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Honoraria; Epizyme: Honoraria; AstraZeneca: Honoraria; BMS/Celgene: Honoraria. Merryman: Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; DG Medicine: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Merck: Research Funding. Munoz: Eli Lilly: Consultancy; AstraZeneca: Consultancy; TG Therapeutics: Consultancy; MEI: Consultancy; Morphosys/Incyte: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Epizyme: Consultancy; ADC Therapeutics: Consultancy; Genentech/Roche: Consultancy, Research Funding; Genzyme: Consultancy; Genmab: Consultancy; Verastem: Consultancy, Research Funding; Aurobindo: Consultancy; Karyopharm: Consultancy; Seattle Genetics: Consultancy, Research Funding; Fosunkite: Consultancy; Alexion: Consultancy; Kyowa: Consultancy; Celgene/Bristol Myers Squibb: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Pfizer: Consultancy; Janssen: Consultancy, Research Funding; Gilead/Kite: Consultancy, Research Funding; Pharmacyclics/Abbvie: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Merck: Research Funding; Portola: Research Funding; Curio: Honoraria; OncView: Honoraria; Physicians' Education Resource: Honoraria; Targeted Oncology: Honoraria; Alexion: Consultancy; BeiGene: Consultancy; Bayer, Gilead/Kite, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium, Novartis, Beigene.: Research Funding; Pharmacyclics/Abbvie, Bayer, Gilead/Kite, Beigene, Pfizer, Janssen, Celgene/Bristol Myers Squibb, Kyowa, Alexion, Fosunkite, Seattle Genetics, Karyopharm, Aurobindo, Verastem, Genmab, Genzyme, Genentech/Roche, ADC Therapeutics, Epizyme, Beigene, Novartis,: Consultancy; Targeted Oncology, OncView, Curio, Genzyme, and Physicians' Education Resource.: Honoraria. Riedell: Cargo Therapeutics: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Intellia Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Research Funding; CVS Caremark: Consultancy, Membership on an entity's Board of Directors or advisory committees; Xencor: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Calibr: Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CRISPR Therapeutics: Research Funding; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sana Biotechnology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Adaptive Biotechnologies: Honoraria. Ryan: Genentech: Other: Institutional research funding; AstraZeneca: Honoraria. Salles: Merck: Consultancy; Kite/Gilead: Consultancy; Ipsen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; BMS/Celgene: Consultancy; Genmab: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Incyte: Consultancy; BeiGene: Consultancy; Molecular Partners: Consultancy; Nurix: Research Funding. Sauter: Cargo Therapeutics: Research Funding; Celgene/BMS: Consultancy; Gamida Cell: Consultancy; Karyopharm Therapeutics: Consultancy; MorphoSys: Consultancy; NKARTA: Consultancy; Ipsen Biopharmaceuticals: Consultancy; Juno Therapeutics: Research Funding; CSL Behring: Consultancy; Precision Biosciences: Research Funding; Actinium Pharmaceuticals: Research Funding; Syncopation Life Sciences: Consultancy; GSK: Consultancy; Bristol-Myers Squibb: Research Funding; Celgene/BMS: Research Funding; Affimed: Research Funding; Kite/a Gilead Company: Consultancy; Ono Pharmaceuticals: Consultancy; NKARTA: Research Funding; Sanofi-Genzyme: Research Funding; CRISPR Therapeutics: Consultancy. Sawalha: Beigene: Research Funding; AbbVie: Research Funding; Genmab: Honoraria, Research Funding; ADC: Consultancy. Wang: Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene, AstraZeneca, Genmab, AbbVie: Other: Advisory Board; Kite: Honoraria; Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab, AbbVie, BeiGene, Merck: Research Funding; InnoCare, AbbVie: Consultancy. Yamshon: Kite: Consultancy; BMS: Consultancy. Zelenetz: BMS/Celgene/Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy; MEI Pharma: Consultancy, Research Funding; Abbvie: Consultancy; Janssen: Consultancy; Adaptive Biotechnology: Consultancy; MorphoSys: Consultancy; Novartis: Consultancy; Genentech/Roche: Consultancy, Research Funding; Gilead/Kite: Consultancy. Palomba: Cellectar: Consultancy; Synthekine: Consultancy; Novartis: Consultancy; Bristo Meyer Squibb: Consultancy. Kumar: Genentech, Inc.: Consultancy, Honoraria, Research Funding; Kite Pharmaceuticals, Janssen: Honoraria; BridgeBio Pharmaceuticals: Current equity holder in publicly-traded company; Loxo Oncology/Lily Pharmaceuticals: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding; Seattle Genetics: Research Funding; Adaptive Biotechnologies, Celgene, Pharmacyclics: Research Funding; Abbvie Pharmaceuticals: Research Funding.

*signifies non-member of ASH