According to findings from a small study published by Calabretta et al in Circulation, treatment with immune checkpoint inhibitors may worsen inflammation in the arteries that distribute blood from the heart.
The research found increased inflammation in the large arteries of 20 Austrian patients with melanoma immediately following treatment with immune checkpoint inhibitors—PD-1 inhibitors, CTLA-4 inhibitors, or a combination of both inhibitors.
“The study provides evidence that [immune checkpoint inhibitor] therapy aggravates present atherosclerosis and treating physicians should consider potential complications here,” said the study's senior author Marcus Hacker, MD, of the Division of Nuclear Medicine at the Medical University of Vienna, in a statement.
“The study provides evidence that [immune checkpoint inhibitor] therapy aggravates present atherosclerosis and treating physicians should consider potential complications here."— Marcus Hacker, MD
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Immunotherapy and Cardiac Issues in Cancer Survivors
Immunotherapy has been shown to be effective for many people with cancers resistant to chemotherapy and radiation. Drugs that block immune checkpoints make it easier for the body's infection-fighting T cells to kill cancer cells—but side effects include potential cardiovascular damage.
People who have cancer are generally at greater risk of dying from cardiovascular disease than the general population. A 2019 study by Sturgeon et al in the European Heart Journal found that over nearly 40 years, more than 1 in 10 cancer survivors in the United States died from some form of cardiovascular disease, most often from heart disease.
While the new study looked at people with just one type of tumor, Dr. Hacker said his team has since expanded its investigation to patients with lymphoma—finding similar results that have not yet published. What's needed next, he said, are studies that look at whether the increased arterial inflammation in people receiving immune checkpoint inhibitors leads to heart problems later in life.
A larger study that tracks patients for 10 or 20 years would be a logical next step, said Carolyn Miller Reilly, PhD, RN, Associate Professor at Emory University's Nell Hodgson Woodruff School of Nursing. She coauthored a recent scientific statement on cardio-oncology.
“The changes they are showing here are not going to immediately demonstrate adverse events,” said Dr. Reilly, who was not involved in the new research. “It's not like we’re going to give this drug, and a month later the patient is going to have a heart attack. But it’s going to cause plaque buildup that can become more unstable. Long-term, we may see the development of cardiovascular disease.”
The study does not suggest patients with cancer—even those with preexisting cardiovascular disease—forgo immune checkpoint inhibitor therapy, Dr. Reilly added, noting that inflammation had worsened most in those with the mildest plaque buildup. “I would not withhold this treatment, as the benefits outweigh the risk,” she said.
Instead, she said, oncologists may wish to consider strategies to mitigate any impact on the heart and consult with a cardio-oncologist to evaluate a specific patient's cardiovascular disease risk. In some cases, medications may also be useful, added Dr. Hacker.
“If our study results can be replicated in prospective settings, we should think about future combination therapies with atherosclerosis-stabilizing agents—like statins—to potentially protect patients at cardiovascular risk from unfortunate events after therapy.”
Disclosure: For full disclosures of the study authors, visit ahajournals.org.
