P21: SUBSEQUENT ANTI-MYELOMA THERAPY AFTER IDECABTAGENE VICLEUCEL (IDE-CEL, BB2121) TREATMENT IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA FROM THE KARMMA STUDY
Authors: P Rodríguez-Otero, J San-Miguel, LD Anderson, S Lonial, A Truppel-Hartmann, J Sanford, E Rowe, TB Campbell, N Munshi
Journal: HemaSphere (2022)

Introduction: Ide-cel, a novel B-cell maturation antigen (BCMA)-directed CAR T cell therapy, showed frequent, deep, and durable responses in triple-class-exposed patients (pts) with RRMM in the phase 2 KarMMa study (NCT03361748; Munshi et al. N Engl J Med 2021). The difference between median progression-free survival (PFS; 8.6 mo) and overall survival (OS; 24.8 mo; Anderson et al. ASCO 2021; poster 8016) prompted analyses examining additional outcomes for pts enrolled in KarMMa, including time to second disease progression (PFS2), type and duration of subsequent anti-myeloma therapy (sAMT), and OS in pts who received sAMT. Methods: Pts with MM, ≥ 3 prior lines of therapy (including an immunomodulatory agent, proteasome inhibitor [PI], and anti-CD38 antibody), and disease refractory to their last regimen per IMWG criteria received ide-cel infusion (target dose range 150–450 x 106 CAR+ T cells) after lymphodepletion (fludarabine 30 mg/m2/day + cyclophosphamide 300 mg/m2/day for 3 days). After ide-cel treatment, pts who relapsed could receive sAMT immediately or following ide-cel re-treatment (R-ide-cel). Results: At a median follow-up of 24.8 mo among surviving pts, 104/128 (81%) pts who received ide-cel had progressive disease or had died. After ide-cel treatment, 68 pts received sAMT alone or with R-ide-cel (11/68 received subsequent anti-BCMA therapy). Fifty-two pts did not receive sAMT or R-ide-cel; of these, 33 relapsed after, or did not respond to, ide-cel and did not receive sAMT; and 19 were not included in this analysis because they were continuing in remission at time of analysis (n = 18) or discontinued without progressive disease or death (n = 1). Eight patients received R-ide-cel alone and were excluded from the analysis. Baseline demographics and clinical characteristics of pts receiving sAMT, anti-BCMA, and no sAMT/R-ide-cel were similar; however, more pts with no sAMT/R-ide-cel had revised International Staging System stage III disease compared with pts who had sAMT or anti-BCMA therapy (33%, 9%, 9%, respectively). The most frequent sAMT classes were corticosteroids (n = 58) and PIs (n = 47); the most frequent sAMT agents were dexamethasone (n = 56) and carfilzomib (n = 32). Anti-BCMA agents included belantamab mafodotin (GSK2857916; n = 10) and teclistamab (JNJ64007957; n = 1). In pts who received sAMT, median PFS and OS after ide-cel were 6.1 and 24.8 mo (Table). Median duration of first sAMT was 44 d and duration of all sAMT was 215 d, with a PFS2 of 13.6 mo (inclusive of time on ide-cel). Among pts who received anti-BCMA therapy, median PFS and OS to ide-cel were 12.1 and 31.0 mo; median duration of first sAMT was 48 d and PFS2 was 15.5 mo. Conclusions: In this descriptive subgroup analysis of the KarMMa trial, the majority of patients who relapsed after ide-cel were able to receive sAMT successfully with a PFS2 intermediate between PFS to initial ide-cel and OS. The PFS2 in this subgroup supports that disease control can be achieved by sequencing of sAMT after relapse from anti-BCMA CAR T therapy. Various classes of anti-myeloma drugs were used as sAMT. Studies are ongoing to define tumor phenotypes prior to and after ide-cel that may correlate with these clinical observations. Previously presented and published: Rodríguez-Otero P, et al. ASH 2021, Blood 2021;138:2743. Study support: 2seventy bio, formerly bluebird bio, and Celgene, a Bristol-Myers Squibb Company.