Early CAR-T Cells expansion is associated with prolonged PFS for patients with RRMM treated with ide-cel: a retrospective monocentric study.

BACKGROUND: The outcome of patients with relapsed and refractory multiple myeloma (RRMM) previously treated with the three main classes of myeloma therapy [immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies] remains poor. Recently, based on the phase II pivotal KarMMa trial [showing prolonged overall survival (OS) and progression-free survival (PFS) among heavily treated patients], idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)- directed chimeric antigen receptor (CAR) T cell therapy has been approved in US for the treatment of RRMM. In France, since June 2021, an early access program has authorized the use of ide-cel in the setting of RRMM (progressive myeloma after at least three previous regimens including the above 3 main anti myeloma therapies).

OBJECTIVES AND DESIGN: We report the first French experience through this early access program in a retrospective study of 24 patients consecutively treated with ide-cel in our institution. The patients were evaluated according to IMWG criteria and by PET-CT 1, 3, 6, 9, and 12 months after ide-cel infusion.

RESULTS: Most of patients had adverse cytogenetic abnormalities and RRMM with triple refractory drugs were seen in 79%. A bridging therapy was required in 19/24 cases. Before CAR-T cells infusion, a Lymphodepletion with fludarabine and cyclophosphamide was systematically performed. The median follow-up was 15.2 months. Three months after ide-cel infusion, 92% and 50% of patients achieved at least a partial response (PR) and a complete response or better (≥CR), respectively. At 6 months, 70% of patients had persistent ≥CR. At 3 and 6 months, bone marrow minimal residual disease (10-6 level) was undetectable in 79% and 75% of cases, respectively. At 6 months, CR assessed by PET-CT was achieved in 15/20 patients (75%). Median PFS was 14.8 months and median OS was not reached. Notably, an expansion of circulating CAR-T cells above 180/mm3 after infusion was strongly associated with prolonged PFS. Additionally, we observed that the level of soluble BCMA measured before infusion was a prognostic factor for PFS and was probably correlated to the tumor burden. A grade 1-2 cytokine release syndrome (CRS) occurred in 22 of 24 patients (92%). Only one patient (4%) experienced a grade ≥ 3 CRS. Occurrence of neurologic toxicity was infrequent (12.5%) and always reversible. Hematological toxicities were relatively common, and secondary hypogammaglobulinemia occurred in most patients. Infections (mostly viral) were frequent but most often non severe.

CONCLUSION: This study echoes the promising KarMMa trial results and identifies possible prognosis indicators in RRMM patients treated with ide-cel, potentially refining treatment strategies and improving outcomes in this challenging context.