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104 Multicenter, Real-World Study in Patients with R/R Large B-Cell Lymphoma (LBCL) Who Received Lisocabtagene Maraleucel (liso-cel) in the United States (US)

Program: Oral and Poster Abstracts
Type: Oral
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Cellular Therapy for B Cell Lymphomas: Prospective Clinical Trials and Real World Data
Hematology Disease Topics & Pathways:
Biological therapies, adult, Research, Lymphomas, Chimeric Antigen Receptor (CAR)-T Cell Therapies, B Cell lymphoma, Clinical Research, Diseases, Therapies, real-world evidence, registries, Lymphoid Malignancies, Human, Study Population
Saturday, December 9, 2023: 9:45 AM

Jennifer L. Crombie, MD1*, Loretta J. Nastoupil, MD2, Charalambos Andreadis3*, Iris Isufi4, Bradley Hunter5*, Allison Winter, MD6, Brian Hess, MD7, Stefan K. Barta, MD8, Michael J. Frigault9, Maria Lia Palomba, MD10, Natalie S. Grover, MD11, Michael D. Jain, MD, PhD12, Tamara K. Moyo, MD13*, Sagar S. Patel, MD14, Priyanka A Pophali, MD15, David Bernasconi16*, Charimar Santiago Parrilla17*, Amani Kitali, MBA, MPH, PMP16*, Fei Fei Liu16*, Mecide Gharibo, MD16* and Marcelo Pasquini, MD, MS17

1Dana Farber Cancer Institute, Boston, MA
2The University of Texas MD Anderson Cancer Center, Houston, TX
3Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA
4Yale University School of Medicine, New Haven, CT
5Intermountain LDS Hospital, Salt Lake City, UT
6Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
7Medical University of South Carolina, Charleston, SC
8Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA
9Massachusetts General Hospital, Boston, MA
10Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY
11The University of North Carolina at Chapel Hill, Chapel Hill, NC
12Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL
13Atrium Health / Levine Cancer Institute, Charlotte, NC
14Transplant and Cellular Therapy Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
15Carbone Cancer Center, University of Wisconsin, Madison, WI
16Bristol Myers Squibb, Princeton, NJ
17Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI

Background: Liso-cel is an autologous, CD19-directed, 4-1BB CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells that has demonstrated efficacy and favorable safety based on clinical studies. Liso-cel is approved in the US for the treatment of adults with R/R LBCL after 1 or more lines of systemic therapy, but data describing outcomes in patients treated with liso-cel in the real-world setting are limited. We report real-world clinical effectiveness and safety of commercial liso-cel in patients with R/R LBCL based on a postmarketing study using data collected at the Center for International Blood and Marrow Transplant Research (CIBMTR).

Methods: This is a noninterventional, observational, multicenter study of US patients who were followed in the CIBMTR Cellular Therapy Registry between February 2021 and November 2022 after infusion with commercial liso-cel (conforming product only) for the treatment of R/R LBCL. Patients who received nonconforming product are being followed in a separate postmarketing study. The primary objective was to evaluate the real-world clinical effectiveness and safety outcomes of patients with R/R LBCL receiving liso-cel, including ORR, CR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and risk of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Results were analyzed and reported descriptively.

Results: At data cutoff (May 4, 2023), 323 patients who received commercial liso-cel across > 50 treatment sites were included in the analysis. The median vein-to-vein time (from leukapheresis to liso-cel infusion) was 36 days (IQR, 34‒42), which is consistent with clinical studies of liso-cel. The median age was 70 years (range, 24‒91). Patients included those with high-risk disease (Table). Most patients had DLBCL not otherwise specified (NOS; 81%), 27% had disease transformed from indolent lymphoma, 12% had high-grade B-cell lymphoma (HGBCL), 37% had International Prognostic Index (IPI) ≥ 3, 6% had active CNS involvement, and 15% had prior transplant. The median number of prior lines of systemic therapy was 3 (range, 0‒11), with 25% of patients having received ≥ 4 lines. The median time from diagnosis to liso-cel infusion was 1.4 years (range, 0.2‒29.7). At a median follow-up of 7.4 months, ORR was 79%, with a 65% CR rate. Median time to response was 1.2 months (IQR, 1.0‒3.1). The median DOR has not been reached; DOR rate at 6 months was 73% (95% CI, 66%‒79%). The median PFS and median OS had not been reached at the time of data cutoff. Estimated 6-month PFS and OS rates were 64% and 82%, respectively. Most events of CRS and ICANS were of low grade, with no CRS and ICANS reported in 48% and 70% of patients, respectively. Overall, 52% of patients had CRS and 3% had grade ≥ 3 events. There was a high concordance on CRS grading per Lee 2014 and American Society for Transplantation and Cellular Therapy criteria. The most common treatments for CRS were tocilizumab (20%) and corticosteroids/tocilizumab (12%). ICANS was seen in 30% of patients, with grade ≥ 3 events in 11%. ICANS was mostly treated with corticosteroids (12%) and corticosteroids/antiepileptics (5%). Based on the attributed cause of death, grade 5 CRS or ICANS were observed in 3 and 3 patients, respectively, and all but 2 patients had concomitant causes of death, including disease progression (n = 3) and hemophagocytic lymphohistiocytosis (n = 2). Prolonged cytopenia (grade 4 thrombocytopenia and/or neutropenia persistent at 30 days postinfusion) occurred in 10% of patients.

Conclusions: This is the first large, multicenter, real-world study of patients with R/R LBCL who received commercial liso-cel in the US. Baseline characteristics of patients treated in the real-world setting were consistent with or worse than the liso-cel registrational study experience, including the percentage of patients who had received ≥ 4 lines of prior systemic therapy (25% vs 26% in TRANSCEND). One-time infusion of liso-cel demonstrated deep and durable responses in patients with R/R LBCL across a broad age range, including those with high-risk features characteristic of poor prognosis. The incidence of severe (grade ≥ 3) CRS and ICANS was low. These results further support liso-cel as a therapeutic option with a favorable benefit/risk profile for a broad, real-world population of patients with R/R LBCL.

Disclosures: Crombie: ADC Therapeutics: Consultancy; Karyopharm: Consultancy; Seagen: Consultancy; Genmab: Consultancy; Dana-Farber Cancer Institute: Current Employment; Kite Pharma: Consultancy; Bayer: Research Funding; Abbvie: Research Funding; Merck: Research Funding; Genetech/Roche: Research Funding; MorphoSys/Incyte: Consultancy. Nastoupil: AbbVie: Honoraria; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Caribou Biosciences: Honoraria, Research Funding; DeNovo: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; Genentech, Inc., Genmab, Gilead/Kite, Janssen, Merck, Novartis, Takeda: Honoraria, Research Funding; Regeneron: Honoraria; AstraZeneca: Honoraria; Gilead Sciences/Kite Pharma: Honoraria, Research Funding. Andreadis: Kite/Gilead: Consultancy; BMS: Consultancy, Other: Grants or contracts ; Novartis: Consultancy, Other: Grants or contracts ; Genentech: Other: Grants or contracts ; Merck & Co., Inc.: Research Funding. Isufi: Incyte: Consultancy; Abbvie: Consultancy; Genmab: Consultancy; Gilead: Consultancy, Current equity holder in publicly-traded company; ADC Therapeutics: Consultancy; Beam Therpauetics: Consultancy. Hunter: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Speakers Bureau; Genmab: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria; Notable Labs: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Speakers Bureau; Genentech: Consultancy, Honoraria; Astellas: Consultancy, Honoraria. Winter: AstraZeneca: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy; BeiGene: Consultancy. Hess: ADC Therapeutics: Consultancy; Bristol Myers Squibb: Consultancy. Barta: Daiichi Sankyo: Consultancy; Affimed: Consultancy; Janssen: Consultancy; Acrotech: Consultancy. Frigault: Kite, BMS, Novartis, Iovance: Consultancy; Kite, Arcellx, Novartis: Research Funding. Palomba: BMS: Honoraria; Cellectar: Honoraria; Kite: Honoraria; Ceramedix: Honoraria; GarudaTherapeutics: Honoraria; Juno: Honoraria, Patents & Royalties; MustangBio: Honoraria; Novartis: Honoraria; Pluto Immunotherapeutics: Honoraria; Rheos: Honoraria; Seres Therapeutics: Honoraria, Patents & Royalties; Smart Immune: Honoraria; Thymofox: Honoraria; Synthekine: Honoraria. Grover: Kite: Honoraria; Genentech: Honoraria; Seagen: Honoraria; Caribou Biosciences: Honoraria; Tessa Therapeutics: Research Funding; Novartis: Honoraria; Sangamo: Current holder of stock options in a privately-held company; Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy, Honoraria. Jain: Myeloid Therapeutics: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Research Funding; Loxo@Lilly: Research Funding; Incyte: Research Funding. Moyo: Kite Pharmaceuticals: Consultancy. Patel: Sanofi: Speakers Bureau; CTi BioPharma: Consultancy; orca bio: Research Funding; Kite Pharma: Speakers Bureau. Pophali: SeaGen: Honoraria. Bernasconi: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Kitali: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Liu: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Gharibo: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Pasquini: Janssen: Research Funding; Novartis: Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Kite Brazil: Honoraria.

*signifies non-member of ASH