Yale Study: CHIP is an independent risk factor for ICI myocarditis

Clonal hematopoiesis of indeterminate potential (CHIP)is an independent risk factor for myocarditis after ICI therapy, a new Yale-led study finds.

CHIP involves mutations in hematopoietic stem cells that can increase the risk of cardiovascular disease and worsen cancer outcomes. The condition is three times as common in the cancer population compared to non cancer population, affecting up to 30-40% of cancer patients.

“ICI myocarditis can affect up to 2% of patients on ICI and could have up to a 50% mortality.” said Jennifer Kwan, MD, PhD, assistant professor of medicine and senior author of the study.

Researchers in Kwan’s lab enrolled 88 patients who were receiving or had previously received ICI therapy: 44 with and 44 without CHIP. The team found patients with CHIP had more than twice the risk of developing myocarditis, more likely to die and had significantly more calcifications of the coronary arteries.

 “We were surprised to find that CHIP could double the risk of ICI myocarditis,” Kwan said. “That’s the same level of risk as the only other known and consistent risk factor for ICI myocarditis, which is being on dual ICI therapy. And even after doing multivariate adjustments, the finding still held.”

Researchers say their findings could impact risk stratification for ICI cancer therapy. “Roughly 50% of patients are eligible for ICI therapy with growing indications, and ICI therapy has offered cancer patients without prior options a potential durable treatment response,” Kwan added. “If CHIP is an independent risk factor for ICI myocarditis, this has implications for who to start on ICI and how frequently they should be monitored. Yet, we currently don’t have any guidelines for screening or monitoring patients with CHIP.”