Clinical outcomes of relapsed/refractory multiple myeloma patients after BCMA-targeted CAR T therapy

Background Anti-BCMA chimeric antigen receptor (CAR) T have shown remarkable efficacy in highly pretreated multiple myeloma (MM) patients. With recent FDA approval of BCMA-targeted CAR T in MM and other agents in late stages of development, CAR T is poised to become more widely used. However, the outcomes of MM patients after relapse on CAR T are largely unknown and effective approaches to salvage after CAR T are urgently needed. Methods Demographics, disease characteristics and post-clinical trial outcomes were collected retrospectively on 31 MM patients who relapsed after CAR T therapy at a single academic hospital. Results 31 MM patients had a median age of 61 years at time of disease progression after CAR T; 19 (61%) were male. Median time from diagnosis to CAR T relapse was 74 months (range 22-282). Post-CAR T follow-up was a median of 391 days (range 86-943). Twenty-six patients (84%) had high-risk cytogenetics. Most patients were highly pretreated with a median of 5 prior lines (range 1-18) and 28 patients (90%) had received autologous stem cell transplant (ASCT). Patient exposure/refractoriness included: lenalidomide (100%/74%), pomalidomide (87%/84%), bortezomib (90%/61%), carfilzomib (94%/87%), CD38-mAb (97%/97%) and alkylating agents (100%/54). Fifteen patients (48%) had received DCEP and four patients (13%) had received prior treatment with a non-BCMA-targeted bispecific Ab. The median time to a subsequent treatment following relapse on CAR T was 34 days (range 0-378). At time of analysis, patients had already received a median of 2 subsequent treatment lines (range 1-8). The most common initial treatment after CAR T relapse was chemotherapy with V-DCEP or VD-PACE (10/29, 34%). Stem cell boost was part of the initial approach in five patients (17%) and was performed in 12 patients at any time after CAR T relapse (41%). Five patients (17%) were treated with bispecific Ab immediately after CAR T and 11 patients (38%) received bispecific Ab therapy at any point after CAR T. Best response to initial treatment varied widely (10 PD, 4 SD, 1 MR, 1 PR, 6 VGPR, 7 CR) with overall response rate (ORR, ≥PR) of 48%. Median time to progression was 104 days for the initial treatment and 62 days for the second line after CAR T. Twenty occurrences of durable responses (>120 days, range 126-513) were observed, of which were 4 selinexor-based treatments, 4 with non-BCMA bispecific Ab, 4 involving stem cell boost and 2 venetoclax-based. At the time of analysis, 17 patients (55%) were alive and the median OS after relapse on CAR T was 496 days. Conclusion Studying the prognosis of patients after relapse and the response to subsequent therapy will provide important clinical insights for salvage, especially as CAR T moves to an earlier treatment setting. At the meeting, we will compare and contrast more mature data on the CAR T cohort with >50 patients that relapsed after bispecific Ab therapy.