Clinical outcomes of patients with multiple myeloma following disease progression after BCMA-targeted CAR T-cell therapy.

Abstract

e20002 Background: While BCMA-targeted CAR T therapies have yielded unprecedented efficacy in patients with multiple myeloma, most patients (pts) experience disease relapse. Treatment after progression on CAR T has become an unmet need given the limited novel treatment options available. We evaluated clinical outcomes for pts relapsing after BCMA CAR T. Methods: This was a single-center retrospective analysis including pts who had been treated with a BCMA-targeted CAR T therapy prior to 12/31/22 and then had disease progression. Data for all subsequent lines of therapy were collected, and best response to therapy was graded as per IMWG criteria. Statistics were descriptive in nature. Results: Thirty pts treated with BCMA CAR T (14 trial, 16 commercial) relapsed. The cohort of median age 61 had notable disease characteristics of 40% with high-risk FISH and 30% with extramedullary disease (EMD). The median number of prior lines of therapy (LOT) was 5, with 80% triple-class refractory and 47% penta-refractory. Patients treated with late BCMA CAR T (≥ 4 prior LOT; n=20) had higher rates of EMD (40% v 10%), triple-class refractory (90% v 60%), and penta-refractory disease (55% v 30%) compared to pts who received early CAR T (< 4 prior LOT; n=10). At data cutoff, 4 pts died without receiving subsequent therapy and 1 pt was pending start of their first regimen. The remaining 25 pts received 58 salvage therapies, of which 54 regimens were evaluable for response. The overall response rate (ORR) for all regimens was 46%. Median overall survival (OS) was not reached, and the 6 and 12-month OS rates were 83% and 77% respectively. ORR and median progression free survival (PFS) stratified by the specific type of salvage therapy are shown in the table. Patients who received a regimen consisting only of agents they had received in a prior LOT had an ORR of 57% and median PFS of 3.6 months. Patients who received early CAR T had a higher ORR to all subsequent salvage therapies (59% v 33%), longer median PFS (4.6 months v 1.6 months), and higher 12-month OS (90% v 70%). Conclusions: For pts with progression after BCMA CAR T, treatment with another BCMA CAR T or transplant had more favorable outcomes. Retreatment with prior therapies resulted in disease control for a fair number of patients, which can serve as a bridge to another novel therapy. The pts treated with early CAR T had more favorable post-progression outcomes than late CAR T, yet 70% of pts who received late CAR T were alive at 1 year post-progression. [Table: see text]