Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Division of Hematology, Mayo Clinic, Jacksonville, FL, USA.
Blood Cancer J. 2024 Jul 23;14(1):122. doi: 10.1038/s41408-024-01081-z.
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.
三类 BCMA 导向疗法（BDT）存在：抗体药物偶联物（ADC）、CAR-T 和 T 细胞衔接器（TCE），每种疗法都有其独特的优势和劣势。为了帮助临床医生在 BDT 之间进行选择，我们回顾了 2018 年至 2023 年间在 Mayo 诊所接受商业或研究性 BDT 治疗的骨髓瘤患者。我们确定了 339 名个体（1 种暴露=297，2 种暴露=38，3 种暴露=4），他们接受了 385 种 BDT（ADC=59，TCE=134，CAR-T=192），中位随访时间为 21 个月。ADC 组患者年龄较大，接受的治疗线数（LOT）更多，且对 penta 难治性疾病的反应较差。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）在调整年龄、髓外疾病（EMD）、pentra 难治性疾病、多打击高危细胞遗传学、既往 BDT 和 1 年内 LOT 数量后的无进展生存期（PFS）分析中具有更好的疗效。同样，与 ADC 相比，CAR-T（aHR=0.28，95%CI=0.18-0.44）和 TCE（aHR=0.60，95%CI=0.39-0.93）的总生存期更长。既往 BDT 暴露对所有类别均有负面影响，但在 CAR-T 中最为明显，ORR 为 86% vs. 50%，中位 PFS 为 13 个月 vs. 3 个月。复发的 54%为髓外性质，其中四分之一的病例无 EMD 病史。CAR-T 显示出更好的疗效，在可行的情况下，应作为初始 BDT。然而，对于既往有 BDT 或疾病快速进展的患者，替代方法可能更为可取。
