This study, through a systematic review and meta-analysis, first integrates interventional and real-world data to comprehensively compare the efficacy and safety of BCMA-targeted CAR-T and BiTE therapies in patients with relapsed/refractory multiple myeloma (R/R MM), providing critical evidence for clinical individualized treatment decisions.
Literature Overview
The article 'Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed/refractory multiple myeloma: a meta-analysis of interventional and real-world studies', published in the Annals of Hematology, reviews and synthesizes the clinical outcomes and safety profiles of BCMA-targeted CAR-T cell therapy and BiTEs (bispecific T cell engagers) in R/R MM. It provides detailed comparisons of overall response rates (ORR), complete response/strings response (CR/sCR), and adverse event characteristics, while incorporating real-world evidence to expand the scope of previous analyses.
Background Knowledge
Multiple myeloma (MM) is a clonal plasma cell malignancy predominantly affecting the elderly, characterized by significant end-organ damage including bone lesions, renal dysfunction, anemia, and hypercalcemia. Despite advancements in treatment modalities such as autologous stem cell transplantation (ASCT), proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies, MM remains incurable, particularly in relapsed/refractory (R/R) stages. B-cell maturation antigen (BCMA), a member of the TNFRSF17 family, is highly expressed on plasma cells and has emerged as a pivotal target for novel immunotherapies. CAR-T cell therapy targets BCMA through ex vivo engineering, activating T cells for potent cytotoxic effects, whereas BiTEs induce T cell-mediated tumor killing by simultaneously binding CD3 on T cells and BCMA on MM cells. However, significant differences exist in efficacy, toxicity, and patient eligibility across these therapies, necessitating further exploration of optimal treatment sequencing, durability of response, and strategies to mitigate toxicity.
Research Methods and Experiments
A systematic search of PubMed, Embase, and Cochrane Library databases up to October 2, 2024, identified 26 studies (2,246 patients with R/R MM), including 15 interventional and 11 observational/retrospective studies. A random-effects model (DerSimonian-Laird method) was employed for meta-analysis, with meta-regression to evaluate the impact of study-specific factors on ORR. Primary endpoints included ORR, CR/sCR, and safety metrics such as hematologic toxicity, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infection rates.
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides the most comprehensive evidence to date on BCMA-targeted immunotherapy for R/R MM, supporting individualized treatment selection based on patient risk profiles and therapeutic goals. Future research should prioritize longitudinal assessments of treatment sequencing, combination regimens, and extended follow-up data to optimize therapeutic strategies and address resistance mechanisms. Expanding real-world evidence will further identify critical clinical determinants of efficacy and safety, advancing precision medicine in MM.
Conclusion
This systematic review and meta-analysis comprehensively evaluates the efficacy and safety of BCMA-targeted CAR-T and BiTEs in R/R MM. CAR-T demonstrates superior depth of remission but carries higher hematologic toxicity and CRS risk, whereas BiTEs offer improved safety at the cost of reduced efficacy. These findings underscore the necessity of tailoring treatment to individual patient characteristics, including age, high-risk cytogenetics, and comorbidities, to inform clinical decision-making. Future research will focus on balancing efficacy and safety with emerging dual-target and combination approaches, while expanded real-world data will refine treatment algorithms and address resistance challenges.
