Use of immunosuppressive treatment
The researchers also examined use of systemic immunosuppression for treating cutaneous toxicities, defined as “a new prescription for systemic glucocorticoids greater than 10 mg per day, prednisone equivalent, or nonsteroidal systemic immunosuppression,” administered within 7 days of the diagnosis of the cutaneous event. They found that 5% of patients overall received systemic immunosuppressive treatment within 7 days of a cutaneous event, which was “at the higher end of what was reported in clinical trials for the treatment of cutaneous toxicities,” Dr. Semenov noted.
“This is likely the result of the delays in diagnosis in nonclinical trial settings ... allowing more time for these events to progress to a higher grade. Also, there may be a greater willingness by providers to initiate systemic immunosuppression due to less stringent treatment protocols in real-world clinical settings,” he said.
Using a multivariable risk prediction model for cutaneous toxicities, the researchers identified use of ipilimumab, a CTLA-4-blocking antibody, as having a protective effect for not developing a cutaneous irAE, compared with the PD-1 blocker pembrolizumab (odds ratio, 0.78; 95% confidence interval, 0.62-0.98; P < .01). But combination ICI therapy (OR, 1.53; 95% CI, 1.25-1.88; P < .001), a melanoma diagnosis (OR, 2.47; 95% CI, 2.11-2.89; P < .001), and a renal cell carcinoma diagnosis (OR, 1.65; 95% CI, 1.36-2.00; P < .001) were found to be risk factors for developing cutaneous irAEs.
“The protective effect of ipilimumab identified in the study is interesting, as historically ipilimumab has been more likely to cause cutaneous toxicities,” Dr. Semenov said. “However, we believe that the majority of this association is mediated by the melanoma, for which ipilimumab was primarily used since its introduction. Independent of this relationship, it seems to be less likely to cause cutaneous toxicity than PD-1 inhibition, according to this data.”
Based on their findings, he said, “dermatologists can utilize this information to facilitate evaluations of high-risk patients so they can take steps to prevent progression to more severe toxicities and reduce reliance or systemic immunosuppression.”
The 25% real-world incidence of cutaneous irAEs observed in the study, Dr. Semenov said, is “somewhat lower than previous clinical trial estimates of over one-third of patients presenting with cutaneous toxicities” but he added that previous estimates were based primarily on studies of patients with melanoma.
That some patients delayed presentation with these conditions “should revise clinicians’ understanding of when to expect patients to present with these toxicities, and not to rule out a delayed onset of symptoms as being unrelated to immunotherapy,” Dr. Semenov said.
Most cutaneous irAEs are ‘manageable’
In an interview, Naiara Braghiroli, MD, PhD, a dermatologist at Baptist Health’s Miami Cancer Institute, Plantation, Fla., who was not an investigator in the study, noted that over the last decade, ICIs have “revolutionized the treatment of metastatic melanoma” and, more recently, the treatment of nonmelanoma skin cancers, with regard to survival rates and side effects.
She said that the results of the study show that “most of the cutaneous side effects are manageable with very few exceptions, like the cutaneous bullous disorders and rarely, more serious reactions [such as] Stevens-Johnson syndrome.”
The majority of the side effects are treatable “and when well controlled, the patient can have a good quality of life” during treatment, she added.
For future research, Dr. Braghiroli noted, it would be interesting to know more about whether the development of any specific cutaneous reaction associated with ICIs “is associated with a higher chance of good antitumor response,” as seen with other anticancer therapies such as epidermal growth factor receptor inhibitors.
Dr. Semenov and Dr. Braghiroli report having no relevant financial disclosures.