Equalizing access to chimeric antigen receptor (CAR) T-cell therapies for myeloma patients

Abstract Introduction: Chimeric antigen receptor (CAR) T-cell therapies targeting B-cell maturation antigen (BCMA) have resulted in improved outcomes for relapsed and refractory myeloma patients. While it is suggested that immune microenvironment, immune response and immune activation may differ by race, whether this has any effect on CAR-T therapy outcomes, or toxicity is largely unknown. This is due in part to limited representation of black patients in pivotal studies that led to CART approvals such as KarMMa-1 (NR), KarMMa-3 (7%), CARTITUDE-1 (18%) CARTITUDE-4 (2.9%), making it difficult to address this question. We evaluated our institutional outcomes to determine whether differential outcomes or toxicities exist by race. Methods: From 2/2018 until 3/2025, of the 191 patients that received commercial CART (ide-cel, N=54, cilta-cel, N=137) at the Winship Cancer Institute of Emory University, 143 patients (ide-cel, N=49, cilta-cel, N=94) received CART for the indication of ≥4 LOT. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board-approved myeloma database and with manual abstraction. The median follow up for idecel (PFS: white vs black: 24.38 vs 27.1 months; OS: white vs black: 25.23 vs 29.37 months) and for cilta-cel (PFS: white vs black: 12.39 vs 8.94 months; OS: white vs black: 13.44 vs 8.94 months). Results: Black patients accounted for 40.4% of the entire cohort (idecel: 39.6% and cilta-cel: 40.9%). The median age at the time of receipt of ide-cel was not different by race (whites vs blacks: 65.3 vs 61.9 (p=0.23), however, for cilta-cel black patients were younger (whites vs blacks: 68.5 vs 61.2 (p=0.008), The ORR and ≥VGPR rates for for ide-cel (black vs white were 71.4% vs 84.2%, p=0.256 and 64.3% vs 78.9%, p=0.227, respectively. For cilta-cel, the ORR and ≥VGPR rates for whites vs blacks were 91.9% vs 82.8% (p=0.23) and 83.8% vs 79.3% (p=0.44), respectively. While the median PFS for white patients treated with ide-cel was 19.45 months, it was not reached for black patients. The 18-month PFS rate for blacks was 67% (p=0.224). The median PFS for patients treated with Cilta-cel was not reached. The 10-month PFS rate for whites vs blacks was 88% vs 86% (p=0.515). The median OS for white patients treated with Ide-cel was 30.75 months, while that of blacks was not reached. The 24 month OS rate was 80% (p=0.263). The median OS for patients treated with Cilta-cel was not reached. The 24 month OS rate for whites vs blacks was 71% vs 80% (p=0.78). For ide-cel, all grade CRS (whites vs blacks: 83% vs 84% p=0.61), including grade 2 or higher (6.9% vs 15.8%, p=0.31), but did not differ by race. However, the rates of CRS were lower for blacks with cilta-cel (whites vs blacks: 74.5% vs 52.6%, p=0.025). Grade 2 or higher CRS rates were 9.1 vs 5.3% (p=0.396). All grade neurotoxicity with Ide-cel (whites vs blacks: 31% vs 21.1% p=0.34), including grade 2 or higher (13.8% vs 10.5%, p=0.55), but did not differ by race. For cilta-cel all grade NTX was 20% vs 13.2%, p=0.28 and grade 2 5.2% vs 2.6% (p=0.458). Day 100 mortality was 10.3% vs 5.3% (p=0.48) for ide-cel and 3.6% vs 5.3% for cilta-cel (p=0.54), did not differ by race. Conclusions: This is one of the largest cohorts that uniformly reviewed the toxicities and clinical outcomes with CART therapies among black patients. While other pooled analysis may be subjected to heterogeneity in the timing for when CART was utilized, the excellent long term outcomes in the current cohort may reflect uniformity of care and the access to therapies after CART relapse. This study emphasizes that accessibility to CART therapy for black patients will result in similar long-term outcomes and level the playing field without additional toxicity. Enriched trials for minorities and focused accrual of minorities in adoptive cellular therapy trials can offer additional insights in the future.