不同的患者、肿瘤和 CAR-T 特征与复发/难治性多发性骨髓瘤中 idecabtagene vicleucel 的起始应答与维持应答相关

Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)-directed autologous chimeric antigen receptor (CAR) T-cell therapy, was studied in relapsed and refractory multiple myeloma after >4 prior lines of therapy in KarMMa (NCT03361748). Translational analyses evaluated patient baseline, tumour and CAR T-cell features associated with initiating and sustaining response to a single ide-cel infusion. Baseline tumour burden, measured by soluble BCMA, and homeostatic cytokine levels released after lymphodepleting chemotherapy were among the top correlates for pharmacodynamic response.

Duration of response was associated with tumour genomic features and quality of engraftment indicated by more robust CD4+ CAR T-cell expansion, higher levels of persistent ide-cel and sustained suppression of BCMA-expressing cells. A working model is proposed whereby patient and microenvironment features that may modulate ide-cel activation and expansion influence the probability of response initiation, and that tumour-intrinsic resistance features and sustained engraftment of ide-cel influence the durability of responses.