Cardiovascular Toxicities of Contemporary Cancer Immunotherapies: A Narrative Review of Immune Checkpoint Inhibitors, Bispecific T-Cell Engagers, and CAR-T Cell Therapies.

Abstract

Immune checkpoint inhibitors (ICIs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cell therapies have produced durable responses across different hematologic malignancies, but each class carries cardiovascular liabilities that differ fundamentally in mechanism, incidence, timing, and mortality risk. A structured narrative review of PubMed/MEDLINE and EMBASE from inception through March 2026 was performed, supplemented by pharmacovigilance data from FAERS and WHO VigiBase, to review and synthesize the available evidence on cardiovascular toxicity and provide a structured comparison of incidence, mechanisms, clinical presentation, outcomes, and monitoring strategies to guide clinical practice. ICI-associated myocarditis is rare (0.06%-1.14%) but carries a case fatality rate approaching 50%, a lethality amplified by combination regimens and obscured by preserved left ventricular ejection fraction in approximately half of presentations. BiTEs may occupy a mechanistically intermediate position: cardiovascular adverse events are reported in 8% to 20% of pharmacovigilance cases, and 83% of these arise without documented concurrent cytokine release syndrome (CRS), implying that their immunopathological profile lies closer to ICI than to CAR-T injury. Bispecific agents are not a homogeneous class: blinatumomab, teclistamab, talquetamab, and elranatamab differ in construct, target antigen, disease setting, CRS frequency, and reported cardiovascular phenotype, and agent-level effects cannot presently be separated from population-level ones. CAR-T cell therapy produces cardiovascular events in up to 19% to 26% of patients, predominantly through IL-6-driven, CRS-coupled hemodynamic injury, with left ventricular dysfunction resolving in the majority following CRS management. Across all 3 classes, foundational clinical trials incorporated no routine cardiac monitoring, current surveillance practices are heterogeneous, and no prospective head-to-head comparative data exist. Each immune therapy class poses a qualitatively distinct cardiac threat at a different point in the treatment course. Risk-adapted surveillance extending beyond the CRS window appears prudent for BiTEs, although this reflects extrapolation rather than validated evidence; serologic and imaging monitoring regardless of systemic symptoms remains essential for ICI recipients; and CRS-guided early intervention is the cornerstone of CAR-T cardiotoxicity management. This review aims to provide clinicians with a comprehensive overview of the cardiovascular toxicities associated with these modern therapies.