Abstract Background Ciltacabtagene autoleucel (cilta-cel) is a BCMA-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory multiple myeloma (RRMM). Following the CARTITUDE-1 results in heavily pretreated patients, the randomized phase 3 CARTITUDE-4 trial demonstrated superior progression-free survival (PFS) and overall survival for cilta-cel compared with standard of care in lenalidomide-refractory patients after one to three prior lines, leading to label expansion in 2024. However, real-world data characterizing outcomes in this earlier-line indication are lacking. Methods We analyzed all patients with RRMM receiving standard-of-care cilta-cel between 2022 and 2025 from the German Registry for Stem Cell Transplantation and Cellular Therapy. Patients were stratified by prior lines of therapy into an Early group (1–3 prior lines) and a Late group (> 3 prior lines). The primary endpoint was PFS. Secondary endpoints included overall response rate, response conversion, and safety outcomes including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), non-ICANS neurotoxicity, and non-relapse mortality. Prognostic associations were assessed using restricted cubic spline Cox regression and univariable Cox models. Results Of 606 patients, 177 (30%) were treated in the Early and 429 (70%) in the Late setting. The overall response rate was 91% and 88%, with complete response in 63% and 54%, respectively. The 12-month PFS was 79% for Early and 70% for Late cilta-cel. Depth of response was the strongest predictor of PFS in both cohorts, with patients maintaining complete response showing 100% PFS at 12 months irrespective of treatment line. Extramedullary disease was adversely prognostic in both groups, whereas high-risk cytogenetics were not associated with inferior PFS in the Early group. Non-ICANS neurotoxicity occurred less frequently in the Early group (3% versus 8%), while non-relapse mortality was comparable (6% versus 7%). Conclusions This analysis demonstrates that cilta-cel in earlier lines of therapy achieves deep responses and high PFS consistent with the CARTITUDE-4 trial. These results provide real-world evidence for the deployment of cilta-cel as early as first relapse and may be a benchmark outside prospective trials.
Gagelmann et al. (Wed,) studied this question.