BCMA CAR-T治疗复发/难治性多发性骨髓瘤患者的长期疗效和影响因素分析

Long-term efficacy and factors influencing BCMA chimeric antigen receptor-T cell treatment in relapsed or refractory multiple myeloma

目的:评价靶向B细胞成熟抗原(B cell maturation antigen,BCMA)嵌合抗原受体T细胞(chimeric antigen receptor-T cell,CAR-T)治疗复发/难治性多发性骨髓瘤(relapsed/refractory multiple myeloma,R/R MM)的长期疗效和安全性。方法:回顾性分析2018年7月至2023年7月在南昌大学第一附属医院接受BCMA CAR-T细胞治疗20例R/R MM患者的临床资料,随访日期截至2023年12月31日。应用Kaplan-Meier生存分析评估患者总生存(overall survival,OS)率和无进展生存(progression-free survival,PFS)率,并统计相关不良反应。结果:20例R/R MM患者,既往中位治疗线数为3(2~6)线,客观缓解率(objective response rate,ORR)为75%,完全缓解(complete response,CR)率为50%;中位随访时间29个月,中位PFS为26个月。10例CR的患者中,5例在末次随访时仍处于缓解状态,缓解持续时间最短为6个月,最长48个月。亚组分析中,髓外浸润、17p缺失遗传学异常和肿瘤高负荷患者PFS显著更差(P<0.05)。细胞因子释放综合征(cytokine release syndrome,CRS)是CAR-T细胞治疗最常见的不良反应,发生率为90%,3~4级CRS的发生率为35%;远期不良反应少,未发生CAR-T细胞治疗相关死亡。结论:BCMA CAR-T细胞是当前R/R MM治疗的有效方案,不良反应可控。髓外浸润和肿瘤高负荷的患者治疗有效,但持久反应欠佳,如何进一步巩固和维持患者的疗效,值得进一步设计前瞻性的临床研究并探究其差异性。

Objective:To evaluate the long-term efficacy and safety of B cell maturation antigen(BCMA)-chimeric antigen receptor-T(CAR-T)cells in the treatment of recurrent/refractory multiple myeloma(R/R MM).Methods:A retrospective analysis was conducted on the clinical data of 20 patients with R/R MM who received BCMA CAR-T-cell therapy at The First Affiliated Hospital of Nanchang University between July 2018 and July 2023.The follow-up period was up to December 31,2023.Overall survival and progression-free survival(PFS)rates were evaluated using Kaplan–Meier analysis,and adverse effects were recorded.Results:Of all 20 cases with R/R MM,the median number of previous treatment lines was three(range:two to six),total objective response rate(ORR)was 75%,and complete response(CR)rate was 50%.The median follow-up duration was 29 months,with a median PFS of 26 months.Among ten patients with CR,five were still in remission at the last follow-up,with the shortest duration of remission being 6 months and the longest being 48 months.In the subgroup analysis,PFS was significantly worse in patients with extramedullary infiltration,high tumor burden,and 17p deletion high-risk cytogenetic features(P<0.05).Cytokine release syndrome(CRS)was the most common(90%)adverse event,and it was mostly mild,with an incidence rate of grade 3 or higher of 35%.Few long-term adverse effects occurred and no CAR-T cell treatment-related deaths were observed.Conclusions:BCMA CAR-T-cell therapy was effective and safe for patients with R/R MM.Patients with extramedullary diseases and high tumor burden can also benefit from this treatment;however,their persistent response is not satisfactory.It is worth exploring the differences and designing prospective clinical studies to consolidate and maintain the efficacy in these patients.