Efficacy and safety of BCMA-directed CAR T-cell therapy in extramedullary relapsed or refractory multiple myeloma: a meta-analysis

Background: 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). Methods: 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). Results: 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. Conclusion: 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.