Follow-up of Chronic Immune-Related Adverse Events After Adjuvant Immunotherapy for High-Risk Resected Melanoma

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In a retrospective cohort study reported in JAMA Network Open, Goodman et al found that patients receiving adjuvant PD-1 inhibitor therapy for high-risk resected melanoma often had chronic immune-related adverse events, with some persisting over long-term follow-up.

Study Details

The study included data from patients who received PD-1 inhibitor therapy for advanced and metastatic melanoma between 2015 and 2022 at six institutions in the United States and Australia who had ≥ 18 months of follow-up after treatment cessation.

Key Findings

The range of follow-up was 18.2 to 70.4 months after PD-1 inhibitor treatment cessation.

Among the 318 patients included in the analysis, 226 (63.7%) developed acute immune-related adverse events during treatment, including 44 (13.8%) with grade 3 to 5 adverse events.

Chronic immune-related adverse events persisting ≥ 3 months after therapy cessation were found in 147 patients (46.2%, 95% confidence interval [CI] = 0.41%–0.52%); of these patients, 74 (50.3%) had grade ≥ 2 events, 6 (4.1%) had grade 3 to 5 events, and 100 (68.0%) were symptomatic.

During long-term follow-up with a median of 1,057 days (interquartile range = 915–1,321 days), 54 patients (36.7%) experienced resolution of chronic adverse events at a median of 11.2 months (95% CI = 8.1–20.7 months) from treatment cessation.

Among 93 patients with persistent adverse events at last follow-up, 55 (59.1%) had grade ≥ 2 events, 41 (44.1%) were symptomatic, 24 (25.8%) were using therapeutic systemic steroids (16 on replacement steroids for hypophysitis [n = 8] and adrenal insufficiency [n = 8]), and 42 (45.2%) were using other management methods.

The most common persistent chronic adverse events were hypothyroidism (n = 38), arthritis (n = 18), dermatitis (n = 9), and adrenal insufficiency (n = 8). A total of 54 patients had persistent endocrinopathies, 48 had nonendocrinopathy events, and 9 (2.8%) had both.

Among 37 patients with chronic immune-related adverse events who received additional immunotherapy, 25 (67.6%) experienced no effect on their chronic toxicity, whereas 12 (32.4%) experienced a flare.

The investigators concluded, “In this cohort study of 318 patients who received adjuvant anti–PD-1 [therapy], chronic immune-related adverse events were common, affected diverse organ systems, and often persisted with long-term follow-up requiring steroids and additional management. These findings highlight the likelihood of persistent toxic effects when considering adjuvant therapies and need for long-term monitoring and management.”

Douglas B. Johnson, MD, MSCI, of the Division of Hematology and Oncology, Vanderbilt University, is the corresponding author for the JAMA Network Open article.

Disclosure: The study was supported by the Burroughs Wellcome Fund, National Cancer Institute, Susan and Luke Simons Directorship for Melanoma, James C. Bradford Melanoma Fund, and Van Stephenson Melanoma Fund. For full disclosures of the study authors, visit

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