Three classes of BCMA-directed therapy (BDT) exist: antibody drug-conjugates (ADCs), CAR-T, and T-cell engagers (TCEs), each with distinct strengths and weaknesses. To aid clinicians in selecting between BDTs, we reviewed myeloma patients treated at Mayo Clinic with commercial or investigational BDT between 2018-2023. We identified 339 individuals (1-exposure = 297, 2-exposures = 38, 3-exposures = 4) who received 385 BDTs (ADC = 59, TCE = 134, CAR-T = 192), with median follow-up of 21-months. ADC recipients were older, with more lines of therapy (LOT), and penta-refractory disease. Compared to ADCs, CAR-T (aHR = 0.29, 95%CI = 0.20–0.43) and TCEs (aHR = 0.62, 95%CI = 0.43–0.91) had better progression-free survival (PFS) on analysis adjusted for age, the presence of extramedullary (EMD), penta-refractory disease, multi-hit high-risk cytogenetics, prior BDT, and the number of LOT in the preceding 1-year. Likewise, compared to ADCs, CAR-T (aHR = 0.28, 95%CI = 0.18–0.44) and TCEs (aHR = 0.60, 95%CI = 0.39–0.93) had superior overall survival. Prior BDT exposure negatively impacted all classes but was most striking in CAR-T, ORR 86% vs. 50% and median PFS 13-months vs. 3-months. Of relapses, 54% were extramedullary in nature, and a quarter of these cases had no history of EMD. CAR-T demonstrates superior efficacy and where feasible, should be the initial BDT. However, for patients with prior BDT or rapidly progressive disease, an alternative approach may be preferable.
目前存在三类BCMA靶向疗法：抗体药物偶联物、CAR-T细胞疗法以及T细胞衔接器，各类疗法均具有独特的优势与局限性。为协助临床医生在BCMA靶向疗法中选择，我们回顾了2018-2023年间在梅奥诊所接受商业化或研究性BCMA靶向治疗的多发性骨髓瘤患者。共纳入339例患者（其中297例接受过1种、38例接受过2种、4例接受过3种BCMA靶向疗法），总计实施385例次治疗（ADC=59例次，TCE=134例次，CAR-T=192例次），中位随访时间为21个月。接受ADC治疗的患者年龄更大、治疗线数更多且多为五药难治性疾病。经年龄、髓外病变存在情况、五药难治状态、多重打击高危细胞遗传学、既往BCMA靶向治疗史及近1年治疗线数调整后的分析显示，与ADC相比，CAR-T（aHR=0.29，95%CI=0.20-0.43）和TCE（aHR=0.62，95%CI=0.43-0.91）具有更优的无进展生存期。同样，在总生存期方面，CAR-T（aHR=0.28，95%CI=0.18-0.44）和TCE（aHR=0.60，95%CI=0.39-0.93）也优于ADC。既往BCMA靶向治疗史对所有疗法均产生负面影响，但对CAR-T的影响最为显著（客观缓解率86% vs. 50%，中位无进展生存期13个月 vs. 3个月）。在复发患者中，54%表现为髓外病变，其中四分之一病例无髓外病变病史。CAR-T疗法展现出更优的疗效，在可行情况下应作为首选的BCMA靶向疗法。然而，对于既往接受过BCMA靶向治疗或疾病快速进展的患者，可考虑采用替代治疗方案。
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