Real‐world outcomes of brexucabtagene autoleucel (brexu‐cel) for relapsed or refractory mantle cell lymphoma (r/r MCL): A CIBMTR subgroup analysis by prior treatment

Introduction: Brexu-cel is a CAR T-cell therapy approved for adult patients (pts) with r/r MCL. In a 3-year follow-up of ZUMA-2 (Wang et al. 2022), ORR was 91% (CR, 68%). Median DOR, PFS, and OS were 28.2, 25.8, and 46.6 mo, respectively. Here, we describe real-world outcomes with brexu-cel analyzed by prior receipt of BTK inhibitor (BTKi), bendamustine, or autoHCT, and 1–2 versus ≥3 prior lines (L) of therapy. Methods: From July 2020 to August 2022, 397 pts who received brexu-cel for r/r MCL in 79 US centers were registered in the CIBMTR observational database. This analysis included 272 pts (median follow-up, 6.6 mo; range, 0.3–16.5), excluding pts with prior non-HCT cellular therapy (n = 7), missing data on prior treatment, or no follow-up. Descriptive analyses were used for all outcomes. Results: Median age was 65.8 y (range, 34.1–84.9); most pts were male (78%). Prior to infusion, 7% had ECOG PS ≥2; 76% had clinically significant comorbidities; 4% had extranodal CNS involvement. At diagnosis, Ki-67 ≥30%, Ki-67 ≥50%, and TP53/17p deletion were reported in 69% (n = 111/160), 44% (n = 70/160), and 19% (n = 29/153) of pts, respectively. Pts had a median of 4L of prior therapy (range, 1–12L; 6% as 2L). Prior to leukapheresis, 87% and 54% of pts had received BTKi or bendamustine, respectively, and 31% were autoHCT recipients. Median time from leukapheresis to infusion was 28 d (IQR, 26–34 d); 18% of pts received bridging therapy. Overall ORR was 89% (CR, 78%). At 6 mo, cumulative incidence of relapse/PD was 21%; DOR, PFS, and OS were 76%, 73%, and 83%, respectively. Grade ≥3 (ASTCT consensus) CRS and ICANS occurred in 9% and 27% of pts, respectively (88% and 62% for any grade). Most CRS (94%) and ICANS (79%) resolved within 3 weeks. Prolonged cytopenia by 30 d occurred in 23% of pts. NRM at 100 d and 180 d were 3% and 6%, respectively, mainly due to infections. ORR in BTKi-naive (n = 36) versus -exposed (n = 233) pts was 85% (CR, 79%; 6-mo DOR, 84%) versus 89% (CR, 77%; 6-mo DOR, 74%); in pts with (n = 145) versus without (n = 124) prior bendamustine was 88% (CR, 75%; 6-mo DOR, 75%) versus 89% (CR, 80%; 6-mo DOR, 77%); in pts with (n = 83) versus without (n = 188) prior autoHCT was 90% (CR, 82%; 6-mo DOR, 83%) versus 88% (CR, 76%; 6-mo DOR, 72%). CR rates were higher in pts with brexu-cel as 2/3L (n = 56) versus 4L+ (n = 213) (91% vs. 74%; ORR, 92% vs. 88%; 6-mo DOR, 77% vs. 75%). Safety profiles were similar regardless of prior BTKi or autoHCT. Pts with prior bendamustine had lower rates of Grade ≥3 ICANS (19% vs. 36%) but higher prolonged cytopenia (29% vs. 16%) versus those without. Conclusions: These early findings suggest that real-world outcomes with brexu-cel are consistent regardless of prior BTKi, bendamustine, or autoHCT. Use of brexu-cel in earlier lines may help achieve a higher CR rate. Further studies with longer follow-up are warranted to contextualize response rates in relation to long-term clinical benefits of brexu-cel. Updated data with longer follow-up will be presented. NA and SK contributed equally. Encore Abstract - previously submitted to ASCO 2023 and EHA 2023 The research was funded by: Kite, a Gilead Company; and NCI grant: National Cancer Institute (CIDR [U24 CA233032]) Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, immunotherapy Conflicts of interests pertinent to the abstract. M. Hamadani Consultant or advisory role: Incyte Corporation, MorphoSys, Kite, Genmab, SeaGen, Gamida Cell, Novartis, Legend Biotech, Kadmon. ADC Therapeutics; Omeros, Abbvie Research funding: Takeda Pharmaceutical Company: ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma N. Grover Consultant or advisory role: Seattle Genetics; Genentech; ADC Therapeutics Stock ownership: Sangamo Honoraria: Novartis Research funding: Tessa Therapeutics M. Shadman Employment or leadership position: Spouse employment for BMS Consultant or advisory role: Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys/Incyte, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune, Mustang Bio, Regeneron, Merck, Fate therapeutics, MEI pharma and Atara Biotherapeutic Research funding: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, AbbVie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, Genmab, Morphosys/Incyte F. L. Locke Consultant or advisory role: A2, Allogene, Amgen, Bluebird Bio, BMS/Celgene, Calibr, Caribou, Cellular Biomedicine Group, Cowen, Daiichi Sankyo, EcoR1, Emerging Therapy Solutions, GammaDelta Therapeutics, Gerson Lehrman Group (GLG), Iovance, Kite Pharma, Janssen, Legend Biotech, Novartis, Sana, Takeda, Wugen, Umoja Research funding: Aptitude Health, ASH, BioPharma Communications CARE Education, Clinical Care Options Oncology, Imedex, Society for Immunotherapy of Cancer Educational grants: A2 Bio J. Gerson Consultant or advisory role: Abbvie, Genentech, Kite Research funding: Loxo M. J. Frank Employment or leadership position: Roche/Genentech Stock ownership: Roche/Genentech L. E. Budde Consultant or advisory role: AstraZeneca, Roche, ADC Therapeutics Research funding: Amgen, Merck, AstraZeneca, Mustang Bio M. Wang Consultant or advisory role: AbbVie, Acerta Pharma, AstraZeneca, BeiGene, BioInvent, Deciphera, InnoCare, Janssen, Kite Pharma, Leukemia & Lymphoma Society, Lilly, Merck, Milken Institute, Oncternal, Parexel, Pepromene Bio, Pharmacyclics, VelosBio Honoraria: AbbVie, Acerta Pharma, AstraZeneca, BeiGene, BioInvent, Dava Oncology, Eastern Virginia Medical School, IDEOlogy Health, Janssen, Kite Pharma, Leukemia & Lymphoma Society, LLC TS Oncology, Medscape, Meeting Minds Experts, MJH Life Sciences, Merck, Moffit Cancer Center, Oncology Specialty Group, OncLive, Pharmacyclics, Physicians Education Research funding: Acerta Pharma, AstraZeneca, BeiGene, BioInvent, Celgene, Genmab, Genentech, Innocare, Janssen, Juno Therapeutics, Kite Pharma, Lilly, Loxo Oncology, Molecular Templates, Oncternal, Pharmacyclics, VelosBio, Vincerx Z. Hu Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead Sciences, Inc. A. Nunes Employment or leadership position: Gilead Sciences Europe, Ltd. Stock ownership: Gilead, Amgen Honoraria: Gilead D. Dalton Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead, Bristol-Myers Squibb I. Kloos Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead Sciences, Inc. D. Lee Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead Sciences, Inc H. Xu Employment or leadership position: Kite, a Gilead Company Stock ownership: Gilead Sciences, Inc M. Pasquini Consultant or advisory role: BMS Research funding: Kite, Novartis, BMS, Janssen, GSK A. Herrera Consultant or advisory role: Karyopharm, Takeda, Tubulis, Regeneron, Genmab, Pfizer, Caribou, Adicet bio, Abbie, BMS, Genentech, Astrazeneca, ADC, Seattle Genetics, Merck Research funding: BMS, Genentech, AstraZeneca, ADC, Merck, Seattle Genetics, Kite, Gilead