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
This article titled '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, systematically reviews and summarizes the application outcomes and safety profiles of BCMA-targeted CAR-T cell therapy and BiTEs (bispecific T cell engagers) in R/R MM. The study details comparative analyses of overall response rate (ORR), complete response/strict complete response (CR/sCR), and adverse reaction characteristics, incorporating real-world study data to expand upon 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 therapeutic advancements involving 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 TNFRSF17 family member highly expressed on plasma cells, has emerged as a critical target for novel immunotherapies. CAR-T cell therapy employs ex vivo-engineered T cells targeting BCMA to mediate potent cytotoxic effects, while BiTEs induce T cell-mediated myeloma cell lysis through simultaneous binding to T cell CD3 and MM cell BCMA. However, significant differences exist between these therapies regarding efficacy, toxicity profiles, and patient eligibility, necessitating further exploration to optimize treatment sequencing, enhance response durability, and minimize toxicities.
Research Methods and Experiments
The study systematically searched PubMed, Embase, and Cochrane Library databases up to October 2, 2024, and included 26 studies (2246 R/R MM patients), comprising 15 interventional and 11 observational/retrospective studies. A random-effects model (DerSimonian-Laird method) was applied for meta-analysis, with meta-regression used to evaluate 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 regarding BCMA-targeted immunotherapy efficacy and safety in R/R MM. It supports individualized treatment selection based on patient risk profiles and therapeutic goals in clinical practice. Future research should evaluate different treatment sequences, combination regimens, and long-term follow-up data to optimize therapeutic strategies and address drug resistance. Expanding real-world evidence will further identify critical clinical factors affecting treatment outcomes, advancing precision medicine applications.
Conclusion
This systematic review and meta-analysis comprehensively evaluated the efficacy and safety of BCMA-targeted CAR-T and BiTEs in R/R MM. CAR-T therapy demonstrated superior depth of response but carried higher risks of hematologic toxicity and CRS, while BiTEs offered safer alternatives with slightly reduced efficacy. Findings emphasize the importance of tailoring treatment selection to individual patient characteristics including age, high-risk cytogenetics, and comorbidities, providing crucial evidence for clinical decision-making. Future research should focus on balancing efficacy and safety through novel dual-targeting approaches and combination therapies, with real-world data continuing to refine treatment strategies.
