Background: B-cell maturation antigen–directed CAR-T cells have revolutionized the therapeutic landscape of relapsed/refractory multiple myeloma (RRMM). Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) received regulatory approval after the pivotal KarMMa and CARTITUDE-1 trials, however, efficacy signals differ and no direct comparison exists. In Austria, these CAR-T products became available considerably later than bispecific antibodies, a fact that likely influenced treatment sequencing and patient selection. Here, we report the first Austrian real-world analysis (RWA) of BCMA-directed commercial CAR-T cell therapy in RRMM, providing country-specific insights and expanding real-world knowledge of how to optimally handle these new therapeutic tools.

Methods: Patients with RRMM who received commercially available ide-cel or cilta-cel between January 2024 and July 2025 in Austria were retrospectively analyzed. Treatment cohorts were defined according to the respective CAR-T product. Co-primary endpoints were overall response rate (ORR) and progression-free survival (PFS). Secondary endpoints comprised overall survival (OS), non-relapse mortality (NRM), and complete response (CR) rate, among others. Prespecified covariates including high-risk cytogenetics, presence of extramedullary disease (EMD), prior exposure to BCMA-directed therapies, and response to bridging therapy (defined as given after T cell apheresis) were evaluated for their impact on clinical outcome.

Results: 87 RRMM patients treated with commercially available BCMA-directed CAR-T cells were included: 46 and 41 patients received ide-cel and cilta-cel, respectively. Patients treated with ide-cel were significantly older than those treated with cilta-cel (median 66 years vs 60 years; p=0.033). In both cohorts, patients received a median of 3 prior lines of therapy, BCMA pre-exposure rates were comparable (17.4% ide-cel vs 19.5% cilta-cel cohort). Other baseline characteristics – including IMWG high-risk cytogenetics, ≥ 2 high-risk aberrations, and EMD – were well balanced. Overall, 92% of patients received bridging therapy; 56.5% of ide-cel and 78.0% of cilta-cel recipients responded to bridging therapy (≥ PR, p=0.038). The ORR after cilta-cel administration was 93,1% compared to 79.5% in patients treated with ide-cel (p=0.206). Cilta-cel treatment resulted in a significantly higher CR rate (65.5% vs 41%; p=0.024). After a median follow‐up of 6.5 months, the 6-month PFS rate of the total cohort was 77% (95% CI: 68−88) with no significant difference between the two CAR-T products (75% ide-cel vs. 80% cilta-cel, p=0.84). The 6‐month OS rate was comparable in both groups with 85% and 84% (p=0.87), respectively. Non-relapse mortality was low (6% in the total cohort) and also comparable between groups. The 6-month PFS rate was significantly higher when ≥ VGPR was achieved after bridging therapy (p=0.043). While prior BCMA-targeting therapy exposure at any time before T cell apheresis (including CAR-T cells, BsAbs and ADCs) did not result in a decreased PFS, BsAb administration immediately prior to apheresis (regardless of targeting BCMA or GPRC5D), was associated with a marked reduction in PFS (p<0.001). Interestingly, patients who received talquetamab as bridging therapy (n=24) experienced a significantly longer PFS (p=0.039) compared to all others. After adjustment for soft tissue EMD, high-risk cytogenetics, response after bridging therapy (< VGPR vs ≥ VGPR), BCMA exposure status, and talquetamab bridging therapy, the CAR-T product remained a non-determining factor for PFS. In multivariate analysis, only treatment with a BsAb prior to T cell apheresis was found to significantly impact PFS (p=0.009).

Conclusion: Unlike other RWA, this first Austrian national RWA on the use of CAR-T cell therapy in RRMM shows no significant difference in PFS when comparing the two commercially available products ide-cel and cilta-cel at a median follow-up of 6.5 months. Treatment with a BsAb immediately prior to T cell apheresis negatively affected PFS after CAR-T infusion and should therefore be avoided. Conversely, bridging therapy with a GPRC5D-targeting BsAb appeared to have a favorable impact on PFS. Prospective analyses of bridging strategies prior to BCMA-directed CAR T-cell products involving BsAbs targeting an alternative antigen, are warranted in order to investigate whether outcomes after CAR T-cell treatment can be improved further.

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2025
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