What is the clinical evidence from this study?

Study design: Review. Population: CAR-T cell therapy-induced cardiotoxicity. Intervention: CAR-T cell therapy.

June 24, 2026Open Access

Chimeric antigen receptor-T cell therapy-induced cardiotoxicity: pathophysiological mechanisms and pharmacological intervention strategies

Key Result

CAR-T cell therapy-induced cardiotoxicity involves acute cytokine release syndrome and long-term immune deficiency, which current pharmacological interventions cannot completely alleviate.

Key Points

This review aims to clarify the pathophysiological mechanisms and pharmacological interventions for CAR-T cell therapy-induced cardiotoxicity.
Systematic review of literature on CAR-T cell therapy and associated cardiotoxicity mechanisms.
Classification of cardiotoxicity into acute and long-term effects.
Summary of clinical pharmacological interventions and preclinical findings.
Acute cardiotoxicity is linked to cytokine release syndrome (CRS), causing hypotension and arrhythmias.
Long-term effects include immune deficiency and myocardial ischemia due to B-cell aplasia.
Pharmacological interventions like IL-6 receptor antagonists showed partial efficacy, but none completely mitigate cardiotoxicity.

Structured PICO

Population

Patients with hematologic malignancies and solid tumors receiving chimeric antigen receptor (CAR)-T cell therapy

Intervention

Pharmacological interventions for CAR-T cell therapy-induced cardiotoxicity (e.g., tocilizumab, emapalumab, ruxolitinib, and preclinical agents targeting IL-1β and TNF-α)

This review outlines the pathophysiological mechanisms of CAR-T cell therapy-induced cardiotoxicity and summarizes current and emerging pharmacological strategies for its management.

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a revolutionary treatment for hematologic malignancies and solid tumors. Multiple approved products and ongoing clinical trials have demonstrated its remarkable antitumor efficacy. However, its clinical application is severely limited by prominent cardiotoxicity, which is closely associated with high morbidity and mortality, posing an urgent clinical challenge. This review systematically elucidates the pathophysiological mechanisms underlying CAR-T cell therapy-induced cardiotoxicity, which can be primarily categorized into acute and long-term adverse effects. Acute cardiotoxicity is driven by cytokine release syndrome (CRS) through macrophage and monocyte activation, endothelial dysfunction, and subsequent myocardial injury, leading to hypotension, reduced left ventricular ejection fraction, and cardiac arrhythmias. Long-term cardiotoxicity is mainly caused by B-cell aplasia-induced immune deficiency and secondary hemophagocytic lymphohistiocytosis, which trigger infectious complications, myocardial ischemia, and apoptosis. We have further summarized clinical pharmacological interventions for such cardiotoxicity, including interleukin (IL)-6 receptor antagonists (tocilizumab), interferon-γ inhibitors (emapalumab), and Janus kinase inhibitors (ruxolitinib). However, none of these drugs can completely alleviate CRS or CAR-T cell therapy-induced cardiotoxicity in all patients. Preclinical agents targeting inflammatory cytokines (IL-1β, tumor necrosis factor-α) and signaling pathways have shown efficacy in ameliorating cardiotoxicity in various animal models. These findings provide novel directions and drug candidates for the treatment of CAR-T cell therapy-induced myocardial toxicity. This review provides a comprehensive theoretical basis for optimizing cardiovascular safety management and developing novel targeted interventions for CAR-T cell therapy.