Medical College of Wisconsin, Milwaukee, WI, United States of America.
Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States of America.
J Geriatr Oncol. 2024 Mar;15(2):101628. doi: 10.1016/j.jgo.2023.101628. Epub 2023 Sep 16.
Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy is transforming the care of patients with relapsed/refractory multiple myeloma (MM). Unfortunately, despite being a disease of older adults these patients remain under-represented in most pivotal clinical trials. We performed a systematic review and proportion meta-analysis of prospective clinical trials and observational studies of anti-BCMA CAR-T therapy in patients with MM with the aim to determine the efficacy and safety of this therapy in older adults (≥65 years).
We searched the Pubmed, Scopus, Web of Science (WOS), Ovid, Embase, CENTRAL, and CINAHL databases through September 9, 2022 and abstracts from the American Society of Hematology (ASH) Annual Meeting 2022. Primary outcome measures included overall response rate (ORR), rates of cytokine release syndrome (CRS), and immune cell-effector-associated neurotoxicity syndrome (ICANS). study was registered with PROSPERO (study number: CRD42022334287).
After screening 2218 references, 14 studies were included for data extraction, with a total of 558 patients, 26.2% (n = 146) of whom were older adults. The pooled ORR amongst this population was 93%, which was comparable to the ORR of 86% amongst younger patients. In older adults, the rates of CRS (any grade) and grade ≥ 3 were 95% and 21%, respectively. For younger patients, the pooled rate of CRS (any grade) and grade ≥ 3 CRS was 91% and 20%, respectively. The rate of ICANS (any grade) in older adults was 15%, which was higher than that observed in those <65 years.
Older adults experience comparable outcomes to younger patients with anti-BCMA CAR-T therapy, albeit with numerically higher rates of neurotoxicity.
抗 B 细胞成熟抗原(BCMA)嵌合抗原受体 T 细胞(CAR-T)疗法正在改变复发/难治性多发性骨髓瘤(MM)患者的治疗方式。不幸的是,尽管多发性骨髓瘤是一种老年疾病,但在大多数关键临床试验中,这些患者的代表性仍然不足。我们对接受 BCMA 靶向 CAR-T 治疗的 MM 患者的前瞻性临床试验和观察性研究进行了系统评价和比例荟萃分析,旨在确定该疗法在老年患者(≥65 岁)中的疗效和安全性。
我们通过 2022 年 9 月 9 日检索了 Pubmed、Scopus、Web of Science(WOS)、Ovid、Embase、CENTRAL 和 CINAHL 数据库,并检索了 2022 年美国血液学会(ASH)年会的摘要。主要观察指标包括总缓解率(ORR)、细胞因子释放综合征(CRS)和免疫细胞效应器相关神经毒性综合征(ICANS)的发生率。该研究已在 PROSPERO(研究编号:CRD42022334287)中注册。
经过筛选 2218 篇参考文献,有 14 项研究纳入数据提取,共纳入 558 例患者,其中 26.2%(n=146)为老年患者。该人群的总体缓解率(ORR)为 93%,与年轻患者的 ORR(86%)相当。在老年患者中,CRS(任何级别)和≥3 级 CRS 的发生率分别为 95%和 21%。对于年轻患者,CRS(任何级别)和≥3 级 CRS 的总发生率分别为 91%和 20%。老年患者的 ICANS(任何级别)发生率为 15%,高于<65 岁患者。
接受 BCMA 靶向 CAR-T 治疗的老年患者与年轻患者的疗效相当,但神经毒性发生率较高。