Disease response at apheresis and association with long-term outcomes following CAR-T cells for relapsed/refractory multiple myeloma (RRMM).
Authors: Thomas Luo, Luca Paruzzo, Sandra P. Susanibar Adaniya, Alfred L. Garfall, Matthew Ho, Shivani Kapur, Marco Ruella, Edward Allen Stadtmauer, Federico Stella, Dan T. Vogl, Adam J. Waxman, Adam D. Cohen
Journal: Journal of Clinical Oncology (2025)

7518 Background: The two approved BCMA-targeted CAR-T products, cilta-cel and ide-cel, have significant efficacy in RRMM, but are not considered curative. Initial studies in ≥4 th line RRMM required progressive disease (PD) at time of enrollment and T cell apheresis. We hypothesized that using CAR-T cells as a planned consolidation strategy (i.e. in patients (pts) with stable or responsive disease on their current therapy) may lead to lower toxicity and better long-term disease control. Methods: We conducted a retrospective review of all RRMM pts receiving commercial CAR-T cells at the University of Pennsylvania from 6/1/21 to 4/30/24, with at least 6 months of follow-up. Intent for consolidation was retroactively assigned by chart review. Kaplan-Meier methodology was used to determine PFS and OS. Results: We identified 149 pts for analysis, with a median follow-up of 14.4 months (mos). Median prior lines was 6 and 81% of pts were triple class-refractory; 46% had high-risk cytogenetics, 26% had extramedullary disease, and 17% had prior BCMA-directed therapy. Pts received either cilta-cel (54%) or ide-cel (46%), and 95% received bridging therapy. CAR-T cells were intended as planned consolidation in 51 pts (34%); of these, 36 (71%) had ≥PR at time of apheresis. For consolidation vs non-consolidation groups, this translated into greater depth of response post-CAR-T cells (≥VGPR, 86% vs. 66%, p=0.01), lower rates of ≥grade 3 CRS (1.9% vs. 9.1%, p=0.16), and longer PFS (median not reached vs. 10 mos, p=0.001), respectively. The PFS improvement was seen for both cilta-cel (p=0.01) and ide-cel (p=0.04). No differences in neurotoxicity were noted. We also performed analyses based on response at apheresis, regardless of intent (8% ≥VGPR, 23% PR, 27% stable disease (SD), and 42% PD). PFS at 20 mos was 88%, 47%, 55%, and 31% for ≥VGPR, PR, SD, and PD at apheresis, respectively (p=0.015). Median PFS of pts with at least SD (≥SD) at apheresis was not reached vs. 9.4 mos in those with PD (p= 0.003), with 20-month OS of 87% in the ≥SD group and 68% in the PD group (p=0.015). Subgroup analysis confirmed this PFS difference for both cilta-cel and ide-cel, while the OS impact was only seen for cilta-cel. On multivariate analysis, having ≥SD at apheresis was an independent predictor for PFS. No statistically significant differences in CRS and ICANS were observed based on response at apheresis. Pts with ≥SD at apheresis had higher absolute lymphocyte counts at days 7 and 14 post-CAR-T infusion than those with PD, indicating disease status at apheresis may be associated with CAR-T product quality. Conclusions: Our data suggest that disease control (≥SD) at time of T-cell collection is associated with more durable responses, supporting use of CAR-T cells as a consolidation strategy in RRMM. We cannot conclude these associations are causal. Further analyses of apheresed T cell characteristics are planned.