Conference Coverage

Rate of cutaneous toxicities from ICIs may be lower than previously reported



A real-world study of patients receiving immune checkpoint inhibitors found that the incidence rate of cutaneous toxicities was 25%, which is lower than previously reported estimates, according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.

What’s more, many of the cutaneous immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) observed in the study may be unreported in clinical trial settings and by providers, according to one of the investigators, Yevgeniy Semenov, MD, MA, a dermatologist at Massachusetts General Hospital, Boston.

“Most cutaneous irAEs are low grade and might go unreported outside of clinical trial settings, as patients might not seek medical care, or when they do, providers might not report them in patient charts. As a result, the diagnoses identified in this study likely represent the most clinically relevant cutaneous events in the ICI population,” said Dr. Semenov, who presented the results at the meeting.

In the study, he said that one of the first issues he and his colleagues encountered was how to classify cutaneous irAEs, as they “can vary widely in morphology and severity.” Immune-related adverse events from ICIs are a “unique constellation of inflammatory toxicities,” affecting nearly every organ system, and may require treatment with immunosuppressive agents that can impact the effectiveness of the ICI. The matter is further complicated by a “lack of definitional standards of what constitutes a cutaneous immune-related adverse event, which greatly limits the research in this area,” Dr. Semenov said. There is also potential for misdiagnosis of irAEs as cutaneous eruptions occurring in patients receiving ICI therapy because of failure to account for the presence of skin disease at baseline, he pointed out.

Dr. Semenov noted that more than 40 cutaneous eruptions have been associated with ICI treatment. “Much of the observational data on cutaneous immune-related adverse events has been riddled with case reports and case series of cutaneous events that happen to be occurring in the setting of ICI therapy. These lack rigorous control groups and often associate events with little to no relationship to the actual ICI, which may have instead occurred in the setting of a competing medication,” he explained.

Real-world data

The researchers thus sought to identify the real-world incidence of cutaneous irAEs with population-level data. Using data from a national claims insurance database from January 2011 through 2019, they compared 8,637 of patients with cancer, treated with an ICI (who had not been treated with other cancer treatments within 6 months of starting an ICI) with 8,637 patients with cancer who were not treated with an ICI, matched for demographics, primary cancer type, and Charlson Comorbidity Index (CCI) score.

In both groups, the mean age of the patients was 67.5 years, 59.2% were men, and 93% had a severe CCI score. The most common cancer types were lung cancer (40%), melanoma (26.6%), and renal cell carcinoma (12.3%). The median follow-up time was 1.9 years, and the median treatment duration was 2.0 years.

Dr. Semenov and colleagues selected 42 dermatoses reported in the literature to evaluate and found an overall incidence of 25% within 2 years of starting ICI therapy. Of those 42 dermatoses, there were 10 with a significantly higher incidence among patients receiving ICIs, compared with controls: drug eruption or other nonspecific eruption (4.2%; incidence rate ratio, 5.00), bullous pemphigoid (0.3%; IRR, 4.91), maculopapular eruption (0.9%; IRR, 4.75), vitiligo (0.7%; IRR, 3.79), Grover’s disease (0.2%; IRR, 3.43), rash and other nonspecific eruption (9.0%; IRR, 2.34), mucositis (1.5%; IRR, 2.33), pruritus (4.8%; IRR, 1.92), lichen planus (0.5%; IRR, 1.75), and erythroderma (1.1%; IRR, 1.70).

After adjusting for a baseline history of squamous cell carcinoma and actinic keratosis, the researchers found that both were significantly less likely in patients receiving ICIs.

A delay in presentation of any cutaneous irAE after starting ICI therapy was also observed (a median of 16.1 weeks), which Dr. Semenov noted was longer than the 5 weeks reported in clinical trials. This delay in presentation increased to a median of 37.5 weeks for the 10 dermatoses with a significantly higher incidence among patients receiving ICIs, with 17.6% of patients presenting in the first month, 63.1% presenting by 6 months, and 84.6% presenting by 1 year.


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