Background: The two commercially available CART constructs targeting BCMA (Ide-cel and Cilta-cel) were approved initially for patients with RRMM after four or more prior lines of therapy (LOT), including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The trials that led to the approval of these constructs differed in patient selection, toxicities and outcomes. Moreover, the absence of head-to-head comparator studies makes the choice of optimal construct fully dependent on investigator discretion. Here, we describe our institutional experience to allow for rational decision making in choosing a CART construct.

Methods: Excluding 62 patients that received investigational CART therapies from 2/2018 until 3/2025, 191 patients received commercial CART (ide-cel, N=54, cilta-cel, N=137) at Winship Cancer Institute of Emory University. 143 patients (ide-cel, N=49, cilta-cel, N=94) received 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. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. The median follow-up for constructs differed, likely from their dates of approval (PFS: ide-cel vs cilta-cel: 25.56 vs 10.54 months; OS: ide-cel vs cilta-cel: 27.1 vs 11.27 months). All results were expressed as (ide-cel vs cilta-cel).

Results: The median age (64.9 vs 66.1 yrs), median time from diagnosis (71.2 vs 79.4 mos), and median prior LOT (6 vs 6) did not differ by the constructs. Other cohort characteristics include male patients (61.2% vs 53.2%), black patients (39.6% vs 40.9%) and high-risk cytogenetics (24.4% vs 28.1%) had no statistically significant differences. Prior therapies include transplant (100% vs 97%), lenalidomide (98% vs 99%), bortezomib (92% vs 96%), pomalidomide (94% vs 94%), daratumumab (92% vs 93%) and carfilzomib (86% vs 84%). Interestingly, 12% vs 13% of patients received prior BCMA therapy. The ORR and ≥VGPR rates were 77.1% vs 88.1% (p=0.09) and 70.8% vs 82.1% (p=0.116), respectively. The median PFS was not reached for both constructs, 18-month estimated PFS-rates were 59% vs 83% (p<0.001) and 2-year OS rate was 73% vs 73% (p=0.46). All grade CRS was higher for ide-cel vs cilta-cel (82% vs 66% p=0.036), and ≥grade 2 CRS was numerically higher (10.2% vs 7.4%, p=0.39). All grade neurotoxicity was higher in ide-cel vs cilta-cel (27% vs 17% p=0.13), including grade 2 or higher (12.2% vs 4.3%, p=0.08). Day 100 mortality rates were 8.2% vs 4.3% (p=0.27).

Conclusion: The higher rates of CRS, neurotoxicity, day-100 mortality was higher for ide-cel likely due to the early availability of ide-cel prior to cilta-cel approval and the usage among patients with high tumor burden. Despite that, both BCMA CARTs (ide-cel and cilta-cel) in the clinical practice setting had better survival outcomes compared to the clinical trial setting, likely from available post-progression therapies. This data suggests prolonged responses and excellent outcomes in the optimal population.

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2025
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