Cardiac Risk Without a Roadmap: Lack of Evidence-Based Guidance for Cardiovascular Toxicity of T-Cell Redirecting...

T-cell redirecting therapies have revolutionized the treatment of several hematologic malignancies. These include CAR T-cell therapy, an adoptive immunotherapy in which a patient's T-cells are engineered to express synthetic receptors against tumor surface antigens, and bispecific T-cell engagers, antibodies simultaneously targeting CD3 and a tumor-specific antigen. Both approaches redirect T-cells toward tumor cells, thereby enhancing anti-tumor immunity independent of major histocompatibility complex class restriction. With expanding indications, their use is extending into older and less fit populations than those represented in pivotal trials, raising important questions regarding toxicity profiles in patients with greater comorbidity burden.

Although cardiovascular toxicities of CAR T and bispecific T-cell engagers have been described, reported incidences are highly variable due to inconsistencies in adverse event definitions and surveillance across studies. Further, most studies have excluded patients with pre-existing heart failure or cardiomyopathy. Consequently, there is a lack of evidence-based guidance for risk stratification, peri-treatment management, or monitoring in this growing subgroup. Here, we briefly review the cardiovascular toxicities associated with T-cell redirecting therapies and highlight limitations in clinical trial inclusion criteria. We then emphasize the urgent need for uniformity in defining cardiovascular toxicities, as well as for dedicated studies in patients with pre-existing heart failure or cardiomyopathy as a distinct high-risk population.