According to the findings of new research, side effects of the cancer drugs Opdivo and Yervoy may increase the risk of serious and potentially life-threatening heart damage.
In a study published this month in the New England Journal of Medicine, researchers from Vanderbilt University warn that a class of cancer drugs known as immune checkpoint inhibitors (ICIs) may be responsible for the deaths of two patients due to a form of heart damage known as fulminant myocarditis.
Opdivo (nivolumab) and Yervoy (ipilimumab) are two members of this class, which are each manufactured and sold by Bristol-Myers Squibb, for treatment of melanoma skin cancer. The patients described in the study were taking the drugs in combination, leading researchers to call for doctors to begin heart testing patients taking any combination of immune checkpoint inhibitors.
Researchers indicate that the two patients developed myositis with rhabdomyolysis, as well as electrical instability in the heart. They also found T-cell and macrophage infiltrates in the hearts of the patients as well.
“Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle,” the researchers report. “Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell–driven drug reaction.”
Myocarditis involves inflammation and damage to the heart muscle, which can be fatal.
Rhabdomyolysis is a side effect associated with several different types of medications, which causes muscle fibers to begin to break down, releasing a protein called myoglobin, which can damage the kidneys as they attempt to filter it out of the bloodstream.
Symptoms of rhabdomyolysis include muscle cramps, tenderness, stiffness, pain or spasms. The illness is usually reported in patients over 65 years of age or those who have renal impairment or uncontrolled hypothyroidism, however these drugs are prescribed heavily to children and young adults. Over time, rhabdomyolysis can lead to kidney damage and even kidney failure. Some may require dialysis or a kidney transplant.
These latest findings come several months after a study by Johns Hopkins researchers linked Opdivo and Yervoy to immune-related adverse events, which could manifest as inflammatory arthritis and sicca syndrome.
Other types of immune responses have been linked to the drugs, which strengthens the chances that the drugs can cause arthritis as well. During the original clinical trials for Yervoy and Opdivo, increased risks were detected for inflammatory bowel diseases, lung inflammation, and other side effects that are considered immune-related.