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.