This study, through systematic review and meta-analysis, first integrated 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 summarizes the application outcomes and safety of BCMA-targeted CAR-T cell therapy and BiTEs (Bispecific T-cell Engagers) in R/R MM. It systematically compares overall response rates (ORR), complete response rates (CR/sCR), and adverse reaction profiles across different therapies while incorporating real-world study data to expand the scope of previous analyses.
Background Knowledge
Multiple myeloma (MM), a clonal plasma cell neoplasm predominantly affecting elderly populations, is 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 highly expressed on plasma cells, has emerged as a key target for novel immunotherapies. CAR-T cell therapy utilizes ex vivo engineered constructs targeting BCMA to activate T cells and mediate potent cytotoxicity, whereas BiTEs induce T-cell mediated tumor killing by simultaneously binding CD3 on T cells and BCMA on MM cells. However, significant differences exist among these therapies regarding efficacy, toxicity profiles, and patient eligibility, necessitating further exploration to optimize treatment sequencing, improve durability of responses, and minimize toxicities.
Research Methods and Experiments
A systematic search of PubMed, Embase, and Cochrane Library databases up to October 2, 2024 identified 26 studies (2,246 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 analysis to assess factors influencing ORR. Primary endpoints included ORR, CR/sCR, and safety parameters 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 treatment sequencing, combination regimens, and long-term follow-up data to refine therapeutic strategies and mitigate resistance. Expanding real-world evidence will help identify critical clinical factors affecting efficacy and safety, advancing precision medicine applications.
Conclusion
This systematic review and meta-analysis comprehensively evaluates the efficacy and safety of BCMA-targeted CAR-T and BiTE therapies in R/R MM. CAR-T demonstrates superior depth of remission but carries higher hematologic toxicity and CRS risk, while BiTEs offer safer administration with slightly reduced efficacy. The findings emphasize treatment personalization based on individual patient characteristics including age, high-risk cytogenetics, and comorbidities. Future research will focus on balancing efficacy and safety through novel dual-targeting approaches and combination therapies, with real-world data playing a pivotal role in optimizing treatment paradigms.
