靶向 BCMA 的 CAR-T 细胞治疗髓外复发/难治性多发性骨髓瘤的疗效与安全性：一项荟萃分析

This meta-analysis systematically evaluated the efficacy and safety of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory multiple myeloma (RRMM) with extramedullary disease (EMD).

PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published up to December 2024 reporting CAR T-cell therapy in RRMM patients with EMD. Studies were screened according to predefined inclusion and exclusion criteria. Data were extracted and the methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) and the MINORS tool; one low-quality study was excluded. A total of 42 studies were included, comprising 242 RRMM patients with EMD and 1,485 without EMD. Fixed- or random-effects models were applied to pool effect sizes. Primary outcomes included objective response rate (ORR), complete response (CR), progression-free survival (PFS), and overall survival (OS). Secondary outcomes included cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

The pooled ORR and CR rates were 79% (95%CI: 71%-86%) and 42% (95%CI: 32%-51%) in the EMD group, and 90% (95%CI: 86%-93%) and 49% (95%CI: 40%-58%) in the non-EMD group, respectively. Reported median PFS ranged from 3 to 18.8 months in the EMD grouPand from 1 to 38 months in the non-EMD group, while median OS ranged from 6 to 13.9 months and from 12.2 to 38 months, respectively. The pooled incidences of grade 3 CRS and ICANS were 18% (95%CI: 8%-27%) and 5% (95%CI: 3%-7%) in the EMD group, compared with 13% (95%CI: 7%-19%) and 6% (95%CI: 2%-9%) in the non-EMD group; none of the differences were statistically significant (P> 0.05). Due to inconsistent reporting and lack of individual patient-level data, hazard ratios and pooled time-to-event analyses were not feasible.

Although RRMM patients with EMD exhibited lower ORR and CR rates than those without EMD, BCMA-directed CAR T therapy demonstrated notable clinical activity with a manageable safety profile. However, no direct comparisons with conventional therapies were performed in this analysis. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42025613422, identifier CRD42025613422.