This study, through a systematic review and meta-analysis, provides the first comprehensive comparison of BCMA-targeted CAR-T cell therapy and BiTEs in patients with relapsed/refractory multiple myeloma (R/R MM) by integrating interventional and real-world evidence. The findings offer critical insights for clinical decision-making in individualized treatment strategies.
Literature Overview
This 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 compares the therapeutic outcomes and safety profiles of BCMA-targeted CAR-T cell therapy and BiTEs for R/R MM. The study systematically evaluates overall response rates (ORR), complete response/strict complete response (CR/sCR) rates, and adverse event characteristics, incorporating real-world data to expand beyond previous analytical scopes.
Background Knowledge
Multiple myeloma (MM) is a clonal plasma cell neoplasm predominantly affecting elderly populations, characterized by end-organ damage including bone lesions, renal dysfunction, anemia, and hypercalcemia. Despite therapeutic advances with 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 key target for immunotherapies. CAR-T cell therapy targets BCMA through ex vivo engineered T cells to induce potent cytotoxic effects, whereas BiTEs activate T cells by dual binding to CD3 on T cells and BCMA on MM cells. However, significant differences exist between these therapies regarding efficacy, toxicity, and patient eligibility, necessitating further exploration to optimize treatment sequencing, durability of responses, and toxicity reduction.
Research Methods and Experiments
A systematic search of PubMed, Embase, and Cochrane Library databases up to October 2, 2024, identified 26 studies (2246 R/R MM patients), including 15 interventional and 11 observational/retrospective studies. Meta-analysis was conducted using a random-effects model (DerSimonian-Laird method), with meta-regression to assess study-related factors affecting 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 evaluate optimal treatment sequencing, combination regimens, and long-term follow-up data to address resistance mechanisms. Expanding real-world evidence will help identify critical clinical factors influencing efficacy and safety, advancing precision medicine in MM care.
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 therapy achieves superior depth of remission but carries higher hematologic toxicity and CRS risks, while BiTEs offer safer administration with moderate efficacy. Clinical decision-making should prioritize patient-specific factors including age, high-risk cytogenetics, and comorbidities. As novel multi-targeted and combination therapies emerge, balancing efficacy-safety profiles will become central to treatment optimization, with real-world data playing a key role in refining therapeutic strategies.
