CELL INTELLIGENCE · 肿瘤细胞治疗研究

Chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has transformed the treatment of relapsed/refractory multiple myeloma (RRMM) but is associated with substantial toxicity. The association between preinfusion disease control and postinfusion toxicity remains underexplored, and no treatment standards exist for bridging therapy in RRMM.

To characterize the holding and bridging regimens used in clinical practice, evaluate their effectiveness in achieving preinfusion disease response, and assess the association between the depth of preinfusion response and the incidence of postinfusion toxicity. STUDY DESIGN: In this single-center retrospective analysis, 88 consecutive RRMM patients received idecabtagene vicleucel (n = 22) or ciltacabtagene autoleucel (n = 66). Preinfusion response was assessed using International Myeloma Working Group criteria. The primary endpoint was a composite of any Grade 2 toxicity across 6 categories: cytokine release syndrome, immune effector cell associated neurotoxicity syndrome, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, early and late immune effector cell-associated hematotoxicity, and infection, evaluated using log-link regression to estimate risk ratios (RR).

Among the 88 patients included in the analysis, the median number of prior lines of therapy was 4. Holding and bridging therapy were administered in 80 (90.9%) and 87 (98.9%) patients, respectively. Twenty-four different therapeutic regimens were administered. Among the 79 patients who received both holding and bridging therapy, 32 (40.5%) changed regimens after apheresis due to insufficient response. Overall, 60/88 patients (68.2%) achieved partial response before infusion. Patients achieving very good partial response (VGPR) had a composite Grade 2 toxicity rate of 8/35 (22.9%) compared with 25/53 (47.2%) in those with <VGPR (RR: 0.48, 95% CI, 0.25-0.95; p = .035); this association persisted in the adjusted model including all 88 patients (adjusted RR: 0.50, 95% CI, 0.26-0.98; p = .042). One case of CAR-T induced Guillain-Barr syndrome and 7 cranial nerve palsies were observed, no parkinsonism occurred. Non-relapse mortality was 2/88 (2.3%). Alkylator-based holding therapy did not lead to an increased number of out-of-specification product.

Deeper preinfusion response was associated with significantly lower toxicity after BCMA-directed CAR-T therapy, identifying preinfusion disease control as a potentially modifiable determinant of toxicity. Intensified holding and bridging strategies were feasible and effective in reducing disease burden in highly pretreated patients, supporting prospective validation of response-adapted bridging to improve the safety of CAR-T therapy in RRMM.