Abstract Idecabtagene vicleucel (Ide-cel) is the first chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell maturation antigen (BCMA) approved by both the European Medicines Agency and the US FDA. Ide-cel has been first available in France since April 2021 through the Early Access Program for treatment of patients (pts) with relapsed/refractory multiple myeloma (RRMM) having received at least 3 therapies including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody and then via commercial access from November 2024. Here we present an update of characteristics and outcomes of pts enrolled in this program. It is a multicenter, retrospective, observational study that included all consecutive pts with RRMM registered in the DESCAR-T database treated with commercial Ide-cel from April 2021 to February 2025. The main objective was to analyze efficacy in terms of response rates, progression-free survival (PFS) and overall survival (OS). Patients' characteristics and outcomes were analyzed according to two periods: cohort A (April-2021 to April-2023, n=175) and cohort B (May-2023 to February-2025, n=596) corresponding to the first two years with limited open center (n=11) and slot availability and the second one, with unlimited access and increased center number (Nb) (n=29). Secondary objectives were evaluation of safety including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICAN), cytopenia, infection, and second primary malignancies (SPM). 915 pts were included of whom 115 (13%) were not infused and 29 were infused after February 2025. Median age of the 771 infused pts (58% male) was 66 years (range: 29-85) and was superior in cohort B (66.9 y) as compared to cohort A (61.7 y). Median Nb of prior lines of therapies was 3 (range: 0-13). More pts had received 2 lines in cohort B (122/596 20% vs 5/175 3%, p0.0001). Revised International Staging System (R-ISS) stage 3 was noted in 21% of pts, 37% had high risk cytogenetic abnormalities defined by del(17p) or t(4;14), and high tumor burden (30% bone marrow plasma cells) was present in 53%, similarly in both cohorts. Triple- (n=559, 73%) and penta-refractory pts (n=168, 22%) were lower in cohort B (69% vs. 83%, p0.0001 and 19% vs. 31%, p=0.01, respectively). Extramedullary disease (EMD) was observed in 73/764 (10%) of pts and was lower in cohort B (45/589, 8% vs. 28/175, 16%). Overall, 162 pts (21%) did not meet at least one of the KarMMa inclusion criteria. 630 pts (82%) had bridging therapy of which 188(34%) responded (106 partial response PR; 50 very good partial response VGPR; 32 complete response CR). Median vein-to-vein time was 56 days (range: 39-357) and was superior in cohort A (61 vs 55 d, p0.0001). Best overall response rate at M3 post Ide-cel was 89% (n=638), including CR, VGPR and PR in 299(42%), 192(27%) and 147(20%), respectively and was similar in both cohorts. In univariate analysis for best response VGPR, only prior BCMA bispecific therapy had a negative impact (odds ratio: 0.35; 95% CI, 0.16 - 0.79). 264 pts (34%) progressed after Ide-cel of which 50% during the first 6 months (m) and 139 pts (18%) died, mostly of disease progression (73%). With a median follow-up after infusion of 11.8 m, median PFS was 14.8 m (95% CI, 12.6 - 16.8) and was similar in both cohorts (hazard ratio: 0.85, p=0.19). Pts achieving VGPR at M3 post Ide-cel had a significantly better PFS (hazard ratio: 1.78; 95% CI, 1.33 to 2.39, p=0.0001). The median OS was 38.9 m (95% CI, 34.2 – NR). In univariate analysis, EMD, ISS, prior bispecific and penta-refractoriness were negative factors for PFS and OS. CRS occurred in 677 (88%) pts (3% grade ≥3). ICAN occurred in 81 (11%) pts (2% with grade ≥3). 453 (59%) pts received tocilizumab in both cohorts. Persistent grade ≥3 thrombocytopenia, anemia and neutropenia at M1 were noted in 218 (28%), 112 (15%) and 378 (49%) pts, respectively. Infections in the first 6 m after Ide-cel occurred in 187 (24%) pts (grade ≥3: 33 18%). 24 pts developed SPM (4 AML and 6 MDS). This large study confirms safety and efficacy of Ide-cel in pts with RRMM in real- world settings across the 4-year period. Response rates, PFS and safety compares favorably to those reported in the registration trial and the real-world studies in the US. Overall, during both periods, selection of less advanced pts leads to a prolonged PFS and OS, never reported to date outside of clinical trial.
Arnulf et al. (Mon,) studied this question.
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