Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Abstract

Immune checkpoint inhibitors are immune stimulatory drugs used to treat many types of cancer. These drugs are antibodies against inhibitory proteins, such as CTLA-4 and PD-1/PD-L1, that are expressed on immune cells. When bound, they allow for increased stimulation of T cells to fight tumor cells. However, immune checkpoint inhibitors have several immune-related adverse effects. Many cases have come to light recently of cardiotoxicity as a result of treatment with these drugs. Cardiotoxicity from immune checkpoint inhibitors is unique due to its rarity and high mortality rate. Patients with this toxicity may present with myocarditis, pericarditis, Takotsubo cardiomyopathy, conduction disorders, and others within just a few weeks of starting immune checkpoint inhibitors. We present here a review of the current research on immune checkpoint inhibitors, their associated cardiotoxicities, the timing of presentation of these conditions, lab tests and histology for each condition, and finally the treatment of patients with cardiotoxicity. We observe a positive skew in the onset of presentation, which is significant for the treating physician.

Keywords: cardiac toxicity; cardiotoxicity; cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors; immune checkpoint inhibitors (ICIs); immune-related adverse events (IRAE); programmed cell death protein 1 (PD-1); programmed death-ligand 1 (PD-L1).

Figure 1

Median weeks until presentation of ICI cardiotoxicity by treatment and cancer type. All cancer types and treatments present within a median of 1–31 weeks after starting treatment.

Figure 2

Median weeks until presentation of ICI cardiotoxicity by treatment and type of cardiotoxicity. All types of cardiotoxicity and treatments present within a median of 1–104 weeks after starting treatment.