Modern multiple myeloma therapies, particularly carfilzomib, induce significant cardiotoxicity through mitochondrial dysfunction and endothelial injury, with all-grade cardiovascular adverse events occurring in 18.1% of patients.
This review highlights the mechanistic pathways of cardiotoxicity from contemporary multiple myeloma therapies and emphasizes the need for personalized cardio-oncology surveillance and risk stratification.
Cardiovascular toxicity has emerged as an important obstacle to realizing the complete clinical potential of contemporary therapies for multiple myeloma (MM), including proteasome inhibitors (PIs), chimeric antigen receptor T-cell (CAR-T) therapies, and CD3-engaging bispecific antibodies. Here, we discuss the epidemiology, underlying mechanistic pathways, and emerging strategies for preventing therapy-induced cardiotoxicity in MM. Based on evidence from multi-omics studies, preclinical models, and real-world observational data, we synthesize the contributions of mitochondrial dysfunction, unfolded protein response (UPR), endothelial injury, and systemic inflammation in cardiac damage throughout treatment strategies. Carfilzomib remains the most cardiotoxic PI, with early subclinical markers such as global longitudinal strain (GLS) worsening and troponin elevation serving as actionable surrogates. For bispecific and CAR-T therapies, cytokine-mediated endothelial dysfunction and activation of immune cells are hypothetical but poorly characterized risk factors for cardiac events. We also evaluate sex, comorbidity index, and population-specific risk as modifiers of cardiotoxic susceptibility. New risk stratification models incorporating omics biomarkers and imaging data are promising but have yet to be broadly implemented in the clinic. Future efforts must emphasize the integration of mechanistic biomarkers into forward-thinking surveillance platforms alongside the tailoring of cardio-oncology protocols to immunotherapy-specific risk profiles. A personalized cardio-oncology approach is necessary to optimize patient outcomes and maintain therapeutic efficacy in the evolving era of MM therapy.
Chatrathi et al. (Fri,) conducted a review in Multiple Myeloma. Multiple myeloma therapies (proteasome inhibitors, CAR-T, bispecific antibodies) was evaluated. Modern multiple myeloma therapies, particularly carfilzomib, induce significant cardiotoxicity through mitochondrial dysfunction and endothelial injury, with all-grade cardiovascular adverse events occurring in 18.1% of patients.