Treatment of Relapsed/Refractory Multiple Myeloma with Ciltacabtagene Autoleucel or Idecabtagene Vicleucel in Racial Minorities-a Multicenter Study

Introduction:

Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are B-cell maturation antigen-directed chimeric antigen receptor T-cell (CAR-T) therapies which have been shown to be effective treatments for patients with relapsed/refractory multiple myeloma (RRMM). Cilta-cel was shown to have an overall response rate (ORR) of 84.6% in the CARTITUDE-4 trial, while ide-cel was shown to have an ORR of 71% in the KarMMA-3 trial. Patient representation among racial and ethnic minorities has historically been low in clinical trials such as these. Only 2.9% of the patients in CARTITUDE-4 were identified as Black or African American. In the KarMMA-3 trial, only 7% of patients were Black and 3% were Asian. This study sought to evaluate outcomes in racial ethnic minorities compared to White patients.

Methods:

We conducted a retrospective multicenter analysis of consecutive patients with RRMM who received cilta-cel or ide-cel between May 2022 and April 2024. 5 centers were included in the analysis, including Levine Cancer Institute, Ohio State University, University of Kansas Medical Center, University of Iowa, and Medical University of South Carolina. Response to treatment was assessed using the International Myeloma Working Group (IMWG) criteria. Baseline characteristics, response rates, progression-free survival (PFS), overall survival (OS), and toxicities were compared. Using R Core Team (2024) software, a descriptive analysis was performed. Continuous variables were summarized and reported the mean (min, max) and median (IQR). Dichotomized factors were summarized by total numbers and frequency. Fisher's exact was used to analyze contingency tables. Wilcoxon rank-sum test was used to compare two independent samples. A univariate Cox proportional hazards analysis assessed the relationship between variables and a time-to-event outcome. The analysis calculated hazard ratios (HRs) and associated confidence intervals (CIs) for each predictor variable, adjusting for censoring in survival data.

Results:

Of the 223 patients who received either cilta-cel or ide-cel for treatment of RRMM, 79% of patients were White, and 21% were racial minorities. The 46 patients who self-reported as racial minorities comprised 2 Asians, 39 Blacks, 2 Hispanics, and 3 patients from other racial groups. Minority patients (MP) were younger at infusion than White patients (WP), with average age 61.3 vs 64.8 years (p = 0.012). 43% of MP were male, vs 59% of WP (p = 0.054). ECOG performance status ≥ 2 was seen in 18.8% of the minority group compared to 7.5% in the White group (p = 0.0795). CrCl <45 mL/min was observed in 22% of MP, compared to 8.5% of WP (p = 0.011). Otherwise, the two groups were similar in demographics, prior therapies, and disease characteristics, including high-risk cytogenetics.

35% of MP received cilta-cel and 65% received ide-cel, whereas 32% of WP received cilta-cel and 68% received ide-cel. The overall best response rate (ORR) at 6-months was 84% for MP compared to 71% for WP. This included sCR in 17% of MP vs 25% in WP, CR 25% vs 17%, VGPR 25% vs 24%, and PR 17% vs 4.7%. Progressive disease was observed in 17% of MP and 26% of WP.

Median follow up of the study population was 27.8 months (IQR 11, N/A). There was no significant difference in PFS (p = 0.8079) or OS (p = 0.4174) between the two groups. The median PFS was 16.1 [95% CI 8.9-N/A] months for MP vs 14.1 [95% CI 11.1-17.1] months for WP, whereas OS was 26.4 [95% CI 16.5 - N/A] months for MP and 27.9 [95% CI 26.3 - N/A] months for WP.

Rates of CRS, ICANS, infections, and hospitalization were similar between the two groups. The incidence of cytopenias was similar, except for neutropenia at 60 days post-infusion, with a median ANC of 1.46 k/ul in MP vs 2.50 k/ul in WP (p = 0.003).

Conclusion:

Patients from racial minorities achieved similar OS, PFS, and ORR compared to WP following treatment with cilta-cel or ide-cel for RRMM. Additionally, toxicities were comparable between these groups. These results suggest that both cilta-cel and ide-cel demonstrate comparable efficacy and safety profiles in patients representing racial minorities in real-world settings. This information is particularly valuable given the historically low enrollment of these patients in clinical trials. Continued assessment of safety and efficacy across a diverse range of racial backgrounds is essential to promote equitable improvement in outcomes for all individuals with RRMM.

Strouse:Poseida: Research Funding; Seagen: Research Funding; Bristol Meyer Squibb: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding. Mushtaq:Iovance Biotherapeutics: Research Funding. Mahmoudjafari:Janssen: Consultancy; Sanofi: Consultancy. McGuirk:Caribou bio: Consultancy; CRISPR therapeutics: Consultancy; Kite: Consultancy; Novartis: Consultancy; Sana technologies: Consultancy; Autolus: Consultancy; BMS: Consultancy; Legend biotech: Consultancy; NEKTAR therapeutics: Consultancy; Envision: Consultancy; Allo Vir: Consultancy. Khan:Amgen: Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; BMS: Research Funding, Speakers Bureau. Ahmed:Legend Biotech: Membership on an entity's Board of Directors or advisory committees; BMS: 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. Bhutani:Caribou Biosciences: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Amgen: Research Funding; BMS: Research Funding; Abvvie: Research Funding.