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Forty-Three Percent of Melanoma Patients Have Chronic Complications from Immunotherapies

Douglas Johnson, MD, MSCI

Chronic side effects among melanoma survivors after treatment with anti-PD-1 immunotherapies are more common than previously recognized, according to a study published March 25 in JAMA Oncology.

The chronic complications, which occurred in 43% of patients, affected the joints and endocrine system most commonly, and less often involved salivary glands, eyes, peripheral nerves and other organs. These complications may be long lasting, with only 14% of cases having been resolved at last follow-up. This finding contrasted with previously reported immunotherapy-related acute complications that affected visceral organs -- including the liver, colon, lungs and kidneys -- which were effectively treated with steroids. However, the vast majority of chronic complications were not severe or life threatening.

"Chronic and long-lasting side effects were more common than we expected and involved a variety of often overlooked organs like the thyroid, salivary glands and joints," said the study's senior author, Douglas Johnson, MD, MSCI, associate professor of Medicine at Vanderbilt University Medical Center and clinical director of Melanoma at Vanderbilt-Ingram Cancer Center.

The retrospective study reviewed the incidence and spectrum of chronic immune-related adverse events in melanoma patients who were treated with adjuvant anti-PD-1 immunotherapies (pembrolizumab or nivolumab) at eight academic medical centers between 2015 and 2020. Chronic complications were defined as those persisting at least 12 weeks after immunotherapy treatments had ended. The study is the first to systematically examine anti-PD-1-related chronic complications in patients with high-risk, resected melanoma.

Most of the chronic complications (96%) were grade 1 or 2 events with no or mild symptoms. The more common complications included adrenal insufficiency, arthritis, dermatitis and thyroiditis.

Rare and acute immune-related adverse events that occur early in the course of treatment with the immunotherapy, such as cardiovascular complications, can be more serious. Johnson and colleagues at Vanderbilt-Ingram first reported in 2016 rare but fatal cardiac side effects from immunotherapies.

"While these side effects are important to monitor and treat, anti-PD-1 therapies remain life saving for many patients with melanoma" Johnson said.

The study's lead author is J. Randall Patrinely, Jr., BA. Other contributing authors from Vanderbilt included Fei Ye, PhD; Ran Fan, PhD and Elizabeth Davis, MD.


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