Predictors of cardiovascular events in multiple myeloma: a systematic review and exploratory meta-analysis

Background Novel therapies have significantly improved survival in patients with multiple myeloma (MM), but cardiovascular (CV) events have become a major challenge, impairing treatment continuity and increasing mortality. This systematic review aimed to identify predictors of CV events in MM to support risk stratification and cardio-oncology management. Methods This review followed PRISMA guidelines and was registered in PROSPERO (CRD420251084727). Five electronic databases were searched from inception to August 2025. Studies reporting multivariable predictors of CV events in MM were included. Methodological quality was assessed using QUIPS tool. Results Eleven studies were included, comprising nine retrospective cohort studies, one prospective observational study, one case-control study. Overall, most studies were judged to be at moderate risk of bias. A total of 20 candidate predictors of CV events were identified. Among these, six were reported in at least two studies, but only hypertension had sufficiently comparable adjusted effect estimates for exploratory meta-analysis. Among treatment-related factors, carfilzomib-based therapy and longer duration of proteasome-inhibitor treatment were associated with a higher risk of CV event in individual studies. Limited evidence from a single prospective study suggests that dynamic natriuretic peptide assessment may have prognostic value, with elevation of natriuretic peptides during the first treatment cycle showing a stronger predictive value (HR 9.5) compared to baseline elevation alone (HR 4.1). Conclusions CV risk in MM appears to be multifactorial, involving both pre-existing vulnerability and treatment-related toxicity. Although several candidate predictors have been identified, the current evidence remains limited by heterogeneity and methodological weaknesses. Larger prospective multicenter studies are required to validate these predictors and to define standardized CV risk assessment and surveillance strategies in MM. Systematic Review Registration identifier CRD420251084727.