Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium.
J Hematol Oncol. 2020 Dec 3;13(1):164. doi: 10.1186/s13045-020-01001-1.
B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T-cell therapy is an emerging treatment option for multiple myeloma. The aim of this systematic review and meta-analysis was to determine its safety and clinical activity and to identify factors influencing these outcomes.
We performed a database search using the terms "BCMA," "CAR," and "multiple myeloma" for clinical studies published between 01/01/2015 and 01/01/2020. The methodology is further detailed in PROSPERO (CRD42020125332).
Twenty-three different CAR-T-cell products have been used so far in 640 patients. Cytokine release syndrome was observed in 80.3% (69.0-88.2); 10.5% (6.8-16.0) had neurotoxicity. A higher neurotoxicity rate was reported in studies that included more heavily pretreated patients: 19.1% (13.3-26.7; I = 45%) versus 2.8% (1.3-6.1; I = 0%) (p < 0.0001). The pooled overall response rate was 80.5% (73.5-85.9); complete responses (CR) were observed in 44.8% (35.3-54.6). A pooled CR rate of 71.9% (62.8-79.6; I = 0%) was noted in studies using alpaca/llama-based constructs, whereas it was only 18.0% (6.5-41.1; I = 67%) in studies that used retroviral vectors for CAR transduction. Median progression-free survival (PFS) was 12.2 (11.4-17.4) months, which compared favorably to the expected PFS of 1.9 (1.5-3.7) months (HR 0.14; p < 0.0001).
Although considerable toxicity was observed, BCMA-targeted CAR-T-cell therapy is highly efficacious even in advanced multiple myeloma. Subgroup analysis confirmed the anticipated inter-study heterogeneity and identified potential factors contributing to safety and efficacy. The results of this meta-analysis may assist the future design of CAR-T-cell studies and lead to optimized BCMA CAR-T-cell products.
B 细胞成熟抗原（BCMA）靶向嵌合抗原受体（CAR）-T 细胞疗法是多发性骨髓瘤的一种新兴治疗选择。本系统评价和荟萃分析旨在确定其安全性和临床疗效，并确定影响这些结果的因素。
我们使用术语“BCMA”、“CAR”和“多发性骨髓瘤”在数据库中进行了搜索，检索了 2015 年 1 月 1 日至 2020 年 1 月 1 日期间发表的临床研究。方法详见 PROSPERO（CRD42020125332）。
迄今为止，已经在 640 名患者中使用了 23 种不同的 CAR-T 细胞产品。细胞因子释放综合征发生率为 80.3%（69.0-88.2）；10.5%（6.8-16.0）有神经毒性。报告的神经毒性发生率在包括更多预处理患者的研究中更高：19.1%（13.3-26.7；I=45%）与 2.8%（1.3-6.1；I=0%）（p<0.0001）。总体缓解率为 80.5%（73.5-85.9）；完全缓解（CR）率为 44.8%（35.3-54.6）。使用羊驼/美洲驼构建物的研究中观察到的 CR 率为 71.9%（62.8-79.6；I=0%），而使用逆转录病毒载体进行 CAR 转导的研究中仅为 18.0%（6.5-41.1；I=67%）。中位无进展生存期（PFS）为 12.2（11.4-17.4）个月，明显优于预期的 1.9（1.5-3.7）个月（HR 0.14；p<0.0001）。
尽管观察到相当大的毒性，但 BCMA 靶向 CAR-T 细胞疗法在晚期多发性骨髓瘤中也非常有效。亚组分析证实了预期的研究间异质性，并确定了安全性和疗效的潜在因素。本荟萃分析的结果可能有助于未来 CAR-T 细胞研究的设计，并导致优化的 BCMA CAR-T 细胞产品。
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