Racial and Ethnic Differences in Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel or Ciltacabtagene Autoleucel

*Authors contributed equally.

Introduction. Two chimeric antigen receptor (CAR) T-cell therapies have been FDA approved for patients with relapsed/refractory multiple myeloma (RRMM): idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). Prior work from our consortium identified racial and ethnic differences in safety and response to ide-cel among patients treated in the standard of care (SOC) setting; despite these differences, survival was similar across race and ethnicity. Here, we extend this work to investigate racial and ethnic differences in safety, efficacy, and outcomes in a larger cohort of patients treated with SOC ide-cel with longer follow-up and patients treated with SOC cilta-cel.

Methods. Data for RRMM patients who underwent leukapheresis by 12/31/2022 and were treated with SOC ide-cel or cilta-cel were pooled across 19 institutions in the U.S. Multiple Myeloma Immunotherapy Consortium. We compared Non-Hispanic White, Non-Hispanic Black, and Hispanic (any race) patients, excluding other racial and ethnic groups due to small sample sizes that precluded sub-group investigations. Separately for each CAR T-cell therapy, racial and ethnic differences in baseline patient characteristics, safety, and treatment responses were examined using chi-square and Kruskal-Wallis rank sum tests. Kaplan-Meier survival curves and log-rank tests were used to examine progression-free survival (PFS) and overall survival (OS) by race and ethnicity.

Results. Among 332 RRMM patients treated with ide-cel, Non-Hispanic Black and Hispanic patients comprised 17% and 10% of the cohort, respectively. Hispanic patients were younger at infusion compared to Non-Hispanic Black and Non-Hispanic White patients (55.5 vs. 63 vs. 66 years, p<0.001). Non-Hispanic Black patients had a higher disease burden (≥ 50% bone marrow plasma cell percentage) compared to Non-Hispanic White and Hispanic patients (35% vs. 20% vs. 19%, p=0.05), while a higher proportion of Non-Hispanic White patients had high-risk cytogenetics compared to Non-Hispanic Black and Hispanic patients (37% vs. 23% vs. 10%, p=0.003). Non-Hispanic Black patients were more likely to develop severe (≥ grade 3) cytopenia at day 30 (p<0.001) and day 90 (p=0.01) post-infusion, and these differences were particularly driven by higher rates of severe neutropenia among Non-Hispanic Black patients at these time points. Non-Hispanic White patients were more likely to achieve a best response of partial response (PR) or better (82%) compared to Non-Hispanic Black (75%) and Hispanic patients (63%, p=0.02). No other racial and ethnic differences in baseline patient characteristics (including cytopenias), safety, PFS, and OS were observed (p>0.05).

Among 222 RRMM patients treated with cilta-cel, Non-Hispanic Black and Hispanic patients comprised 12% and 9% of the cohort, respectively. At baseline, Non-Hispanic Black and Hispanic patients were more likely to have anemia (p=0.01), and Non-Hispanic Black patients were more likely to have thrombocytopenia (p=0.02) and neutropenia (p=0.06) compared to Non-Hispanic White patients. No other differences in baseline patient characteristics were observed by race and ethnicity. While not statistically significant, a higher rate of severe (≥ grade 3) cytopenia at day 90 post-infusion was observed among Non-Hispanic Black and Hispanic patients compared to Non-Hispanic White patients (33% vs. 44% vs. 21%, p=0.07), similar to the ide-cel cohort. This finding was primarily driven by higher rates of severe neutropenia among Non-Hispanic Black patients and higher rates of anemia among Hispanic patients. No other racial and ethnic differences in safety, responses to cilta-cel, PFS, or OS were not observed in the cilta-cel cohort (p>0.05).

Conclusion. In a large cohort of RRMM patients treated with SOC ide-cel or cilta-cel, we observed a higher rate of cytopenias post-infusion and inferior ide-cel responses among racial and ethnic minority patients compared to Non-Hispanic White patients. Despite these differences, survival was similar across race and ethnicity, suggesting that both available CAR T-cell therapies for RRMM patients can be utilized across all populations. Future studies that include larger patient cohorts of racially and ethnically diverse patients should be conducted to confirm these findings and additionally evaluate long-term outcomes.

Peres:Bristol Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding. Sidana:Regeneron: Consultancy; BiolineRx: Consultancy; Legend: Consultancy; Takeda: Consultancy; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding; Abbvie: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Novartis: Research Funding; Kite, A Gilead company: Consultancy; BMS: Consultancy, Research Funding. Afrough:K36 Therapeutics: Research Funding; Bristol-Myers Squibb: Honoraria, Other; Karyopharm Therapeutics: Honoraria, Other; Sanofi: Honoraria, Other; Adaptive Biotech: Research Funding; Abbvie: Research Funding. Shune:BMS: Membership on an entity's Board of Directors or advisory committees; Norvatis: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Midha:Janssen: Consultancy; Pfizer: Consultancy. Castaneda:BMS: Consultancy; Janssen: Consultancy; Legend Biotech: Consultancy. Ferreri:Sanofi: Consultancy; Janssen: Consultancy; Affimed Therapeutics.: Current equity holder in private company. Davis:Janssen Biotech: Speakers Bureau. Blue:Sanofi: Speakers Bureau; Pfizer Pharmaceuticals, Oncopeptides, Takeda, Abbvie, Janssen, and Kite Pharmaceuticals: Consultancy. McGuirk:Sana technologies: Consultancy; Caribou bio: Consultancy; CRISPR therapeutics: Consultancy; NEKTAR therapeutics: Consultancy; Autolus: Consultancy; Envision: Consultancy; Allo Vir: Consultancy; Novartis: Consultancy; Kite: Consultancy; BMS: Consultancy; Legend biotech: Consultancy. Wagner:Pfizer: Consultancy; Jazz: Research Funding. Bansal:Kite Pharma: Other: Travel Support. Mikkilineni:Legend Biotech: Consultancy, Other: advisory board at ASH December 2023; BiolineRx: Consultancy, Other: advisory board at ASH December 2023. Kaur:Pfizer: Consultancy, Honoraria; Arcellx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectar Biosciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Research Funding. Gaballa:Boxer Capital, LLC: Consultancy; GLG: Consultancy; Guidepoint: Consultancy; Bristol Myers Squibb: Consultancy. 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Dhakal:Acrellx: Research Funding; Sanofi: Research Funding; Genentech: Consultancy, Honoraria; C4 therapeutics: Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Medical College of Wisconsin: Current Employment; Carsgen: Research Funding; Pfizer: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau. Khouri:Janssen: Consultancy; Legend Biotech: Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; GPCR Therapeutics: Honoraria. Raza:Pfizer: Consultancy, Honoraria; Prothena Biosciences: Consultancy; Kite Pharma: Consultancy. Reshef:Sana Biotechnology: Consultancy; Sanofi: Research Funding; Bayer: Consultancy; J&J: Research Funding; Takeda: Research Funding; Immatics: Research Funding; BMS: Research Funding; Synthekine: Research Funding; Cabaletta: Research Funding; Atara Biotherapeutics: Research Funding; Genentech: Research Funding; TCR2: Research Funding; Abbvie: Research Funding; Precision Biosciences: Research Funding; Quell Biotherapeutics: Consultancy; Autolus: Consultancy; Gilead Sciences: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; TScan: Consultancy, Research Funding; Orca Bio: Consultancy; CareDx: Research Funding; Allogene: Consultancy. Alsina:Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. 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Martin:AMGEN: Research Funding; Janssen: Research Funding; BMS: Research Funding; Sanofi: Research Funding; Pfizer: Honoraria; Roche: Honoraria; GSK: Honoraria. Voorhees:Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lava Therapeutics: Consultancy; GSK: Consultancy, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; Janssen: Consultancy, Research Funding. Patel:Merck: Consultancy; Abbvie: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; Oricel: Consultancy, Other: Chair of scientific board; Kite, A Gilead company: Consultancy, Other: scientific advisory board; AstraZeneca: Consultancy; Johnson & Johnson (Janssen): Consultancy; BMS: Consultancy, Other: chair of scientific advisory board ; Genentech: Consultancy; Caribou Sciences: Consultancy; Poseida: Consultancy. Hansen:Karyopharm: Consultancy, Research Funding; Pfizer: Consultancy; BMS: Consultancy, Research Funding; Janssen: Consultancy. 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