Melanoma subtype influences immune-related adverse events in ICI therapy

Cutaneous immune-related adverse events are highly dependent on melanoma subtype among immune checkpoint inhibitor therapy recipients, according to a study.

According to Nga Nguyen, MD, MPH, of the department of dermatology at Massachusetts General Hospital in Boston, and colleagues, evidence has shown that the occurrence of cutaneous immune-related adverse events (cirAEs) may be related to improved survival among recipients of immune checkpoint inhibitor (ICI) therapy. This is especially true of those ICI therapy recipients with melanoma, the researchers wrote.

“However, benefits of ICI therapy have not been consistent across all melanoma subtypes,” Nguyen and colleagues continued, “with worse response in patients with acral, mucosal and uveal disease.”

In this retrospective, multi-institutional, cohort study, researchers examined the impact of melanoma subtypes on cirAE onset and survival among ICI therapy recipients.

For this study, a total of 747 ICI recipients were categorized into their respective melanoma subsets which included acral melanoma, mucosal melanoma, uveal melanoma, nonacral cutaneous melanoma and melanoma of unknown primary. Among the patients, 31.6% developed a cirAE.

Results showed that cirAE incidence and morphologic distribution were highly dependent on melanoma subtype. The researchers used the nonacral cutaneous melanoma cohort as the control group. Patients with acral melanoma were less likely to develop a cirAE (HR = 0.41; 95% CI, 0.2-0.85) compared with the nonacral cutaneous melanoma group; however, after covariate adjustment, there was no significant difference in cirAE development vs. the control group in the other three melanoma subsets.

Overall, mucosal melanoma patients exhibited the highest cirAE incidence rate at 41.2%, followed by nonacral cutaneous melanoma (32.2%), melanoma of unknown primary (31.6%), uveal melanoma (18.8%) and acral melanoma (15.7%).

Vitiligo (50%) was identified as the primary presentation in acral melanoma patients, whereas lichenoid dermatitis was more prevalent in nonacral (5.2%) and unknown primary (6.5%) melanomas.

Additionally, vitiligo was found to provide protection from mortality (HR = .42; P = .094). Isolated pruritus without visible manifestation of rash (HR = 0.56; P = .052), maculopapular eruption (HR = 0.60, P = .018) and nonspecific rash (HR = 0.46; P = .001) were also associated with lower risk for mortality compared with those patients without cirAEs.

Although cirAEs were associated with reduced mortality across all melanoma subtypes (HR = 0.76; P = .042), patients with acral (HR = 2.04; P = .005), mucosal (HR = 2.3; P < .001) and uveal (HR = 4.09; P < .001) primaries exhibited the worst survival compared with the control group, even with ICI therapy.

“Our study supports increasing evidence that cirAEs are associated with improved overall survival among melanoma patients, which underscores the need for effective and supportive patient care interventions that would permit the maintenance of quality of life and dose intensity of ICI therapy while managing these toxicities,” Nguyen and colleagues concluded.