(PA-038) Optimizing the Use of Chimeric Antigen Receptor T-cell (CART) Therapy for Relapsed/refractory Myeloma

Introduction: Chimeric Antigen Receptor T-cell (CAR-T) therapies have changed the treatment landscape of relapsed and/or refractory myeloma (RRMM), with two commercially available anti-BCMA CAR-T now approved in early relapse. The optimal use and choice of construct is still debatable, and here we describe our institutional experience to optimize the use and indication.

Methods: 248 patients received 253 CAR-T therapies targeting BCMA from 2/2018 until 3/2025 at Winship Cancer Institute of Emory University. 60 (23.7%) were administered on trial and were excluded from analysis. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board-approved myeloma database and with manual abstraction. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. The median follow-up for the entire cohort for PFS was 10.5 months (Ide-cel and Cilta-cel was 25.2 vs 8.1 months) and for OS was 12.45 months (26.3 vs 8.1 months)

Results: 193 patients received commercial constructs: 29%  Ide-cel and 71%  Cilta-cel. The median age is 65.4 (range, 29-86). 57% are male and 38.3% are black.  Most patients (74.6%) received ≥4 PLOT including 97% with prior transplant. Only 9.4% of this cohort previously received prior BCMA therapy. The ORR and ≥VGPR rates are 77.8% and 72.2% for Ide-cel, and 88.3% and 83% for Cilta-cel, respectively. The ORR and ≥VGPR rates for patients with ≥4 PLOT for Ide-cel vs Cilta-cel are 77.1% vs 88.1% and 70.8% vs 82.1%, respectively (p=NS). The median PFS for patients treated with Ide-cel was 46.3 months while that for Cilta-cel was NR, due to shorter follow up (16-month PFS 86.7%). For those with ≥4 PLOT, estimated 16-month PFS is  59% vs 83% for Ide-cel vs Cilta-cel. The 2-year OS rate for patients treated with Ide-cel vs Cilta-cel was 72% vs 76% (p=NS). For those with ≥4 PLOT, 2-year OS rate for patients treated with Ide-cel vs Cilta-cel was 71% vs 73% (p=NS). All grade CRS was higher in Ide-cel vs Cilta-cel (82% vs 66% p=0.031), though no statistically significant difference in grade 2 or higher CRS. All grade neurotoxicity was higher in Ide-cel vs Cilta-cel (28% vs 17% p=0.093), including grade 2 or higher (12.5% vs 2.9%, p=NS).

Conclusions: Though earlier administration of both BCMA CAR-T cell therapies is becoming increasingly common, these data demonstrate impressive efficacy in both late relapse and real world setting as compared to clinical trial data. This improvement might be attributable to improved bridging therapies available at this time, as well as careful patient selection. Of note, early Ide-cel use prior to Cilta-cel approval was often administered to patients with significant tumor burden potentially explaining the increased CRS and neurotoxicity. This data suggests prolonged responses and excellent outcomes in the right patient population.