Matthew Shinkle , 2025-04-17 15:46:00
April 17, 2025
3 min read
Key takeaways:
- Chronic cutaneous immune-related adverse events often persist more than a year after discontinuation of immune checkpoint inhibitor therapy.
- The findings highlight the importance of dermatology referral.
Cutaneous immune-related adverse events that develop after immune checkpoint inhibitor therapy become chronic in nearly one-quarter of cases, according to a research letter published in JAMA Dermatology.
These chronic events often persist more than a year after immune checkpoint inhibitor (ICI) discontinuation, results showed.
Data derived from Fletcher KA, et al. JAMA Dermatol. 2025;doi:10.1001/jamadermatol.2025.0025.
Cutaneous immune-related adverse events (cirAEs) are a common complication of ICI therapy. Acute events can become chronic; however, that process is not well understood, according to study background.
“We had noticed that some patients were experiencing lingering types of toxicities,” Douglas B. Johnson, MD, MSCI, professor of medicine and leader of the melanoma clinical research program at Vanderbilt University Medical Center, told Healio.
Johnson and colleagues since published work that showed approximately 40% of patients had adverse effects lasting at least 3 months after treatment discontinuation.
In their current study, Johnson and colleagues sought to evaluate histological and clinical characteristics of chronic cirAEs, as well as symptom duration, treatments and outcomes, among patients treated with ICIs between 2015 and 2022.
Researchers reviewed data from 318 participants in a prior study who received ICIs in the adjuvant setting. They supplemented the cohort with patients treated with ICIs in the adjuvant or metastatic setting at Vanderbilt’s oncology and dermatology clinics.
All patients received at least one dose of nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck) or ipilimumab (Yervoy, Bristol Myers Squibb).
The researchers classified chronic cirAEs as those that developed during ICI therapy or within 3 months of ICI discontinuation and continued for more than 3 months after ICI discontinuation.
Nearly one-third (31%; n = 100) of the patients treated on the prior study developed cirAEs. Those events became chronic for 24 patients, or 7.5% of all patients treated on study.
Fletcher and colleagues’ analysis included 52 patients (median age, 66.5 years; 62% men) with chronic cirAEs — 21 who had been treated on the prior study and had detailed follow-up, and 31 treated at Vanderbilt clinics. The majority (88%; n = 46) received ICI monotherapy.
Chronic cirAEs persisted for a median 629 days (range, 203-2,270) total and a median 446 days (range, 119-2,270) after ICI discontinuation.
Results showed 44 patients (85%) had grade 1 or grade 2 cirAEs, and seven patients (14%) had grade 3 cirAEs. Clinical manifestations included pruritus, morbilliform eruptions, dermatitis and bullous pemphigoid-like eruptions.
Treatments included supportive care, topical and systemic corticosteroids, and biologics.
Forty-one patients (79%) experienced cirAE resolution during follow-up. However, a majority of patients had cirAEs persist for 12 months (79%; n = 41), and more than half had cirAEs persist for 18 months (54%; n = 28).
“Incidence of [chronic cirAEs among all patients treated on the prior study] ended up being 7% to 8%, which I roughly expected,” Johnson said. “What was surprising was when we pulled in a more severe group of patients, the average duration of chronic side effects was more than a year.”
Researchers acknowledged study limitations. For example, the dermatology cohort included more severe cases and more patients who received biologics. In contrast, researchers noted the potential for “nonspecific morphological descriptions and distinct management” in the non-dermatology cohort.
The findings highlight the importance of long-term patient follow-up with dermatologists who understand how to treat cirAEs, Johnson said. This may help some cutaneous immune-related events from becoming chronic, he added.
“There’s a fair number of patients who have low- to intermediate-grade skin toxicities even while on treatment,” Johnson said. “You don’t want to stop therapy altogether, but some conservative measures [may not] help that much.”
Side effects may get better or resolve by simply stopping ICI therapy, Johnson said, but that is not a guarantee.
“Most do, so I think we have it in our minds that they should, but that’s not always the case,” he added. “For some patients [for whom] the side effects are minor, they seem to be continuing or even getting worse after stopping treatment. Dermatology referral is important.”
For more information:
Douglas B. Johnson, MD, MSCI, can be reached at douglas.b.johnson@vumc.org.
Sources/Disclosures
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Disclosures:
Johnson reports receiving grants from James C. Bradford Melanoma Fund, NCI and Van Stephenson Melanoma Fund, as well as personal fees from AstraZeneca, Bristol Myers Squibb, Jackson Laboratories, Merck, Novartis, Pfizer and Teiko. Please see the study for all other authors’ relevant financial disclosures.