In rare cases, cancer immunotherapy drugs may be encouraging T cells to attack the body's own organs, scientists say. Image by Patrick J. Lunch/Wikimedia Commons

NASHVILLE, Nov. 3 (UPI) -- Two cancer immunotherapy drugs may cause rare and sometimes fatal cardiac side effects, Vanderbilt University Medical Center researchers report.

The drugs, called ipilimumab and nivolumab, have both been approved by the U.S. Food and Drug Administration for immunotherapy treatment. The approach aims to stimulate anti-tumor responses in cancer patients using their own immune system.


However, two cases detailed in a report in the New England Journal of Medicine indicate the two drugs may have severe drawbacks.

Researchers examined the cases of a 65-year-old woman and a 63-year-old man, both with metastatic melanoma, who were each hospitalized nearly two weeks after beginning the immunotherapy treatment.

"The patients came with rather vague symptoms including fatigue and muscle aches. What made us take notice, however, were blood tests for cardiac damage that were extremely elevated and the electrocardiograms (EKG) that were abnormal in both cases," Dr. Javid Mosleshi, director of the Cardio-Oncology Program at VUMC, explained in a press release. "The problems quickly advanced such that the patients each needed a pacemaker to control the heart's electrical activity. The degree of cardiac arrhythmia was striking."

According to the authors, the checkpoint inhibitors responsible for influencing anti-tumor responses can cause fatal myocarditis, an inflammation of the heart muscle.

Both patients died, and Justin Balko of the Vanderbilt-Ingram Cancer Center said autopsies and biopsies of the cardiac tissue clearly indicated an immune reaction to the heart.

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VUMC pathologists found robust T cell and macrophage infiltrates. Shared populations of invasive T cells were identical to those in the tumors and skeletal muscle. Balko said the drugs may be turning the immune response intended for cancer against the body's own organs.

"One hypothesis based on the data is that essentially the body is seeing the heart and muscle tissue as foreign, just like the tumor," he explained. "This gives us a starting point to develop a model to see how consistent this is with other cases as they appear and once we have that model, determine the right way to intervene so that we can keep other patients safe."

Researchers admit these cases are rare, and occur in less than 1 percent of cancer patients treated with the drugs. They recommend additional studies to develop better treatment strategies.