Cutaneous Immune-Related Adverse Events Improve Survival in Melanoma

Even after excluding vitiligo, cirAE development remains associated with better survival among all ICI recipients.

Patients with advanced cancer, especially melanoma, who receive immune checkpoint inhibitors (ICIs) and experience cutaneous immune-related adverse events (cirAEs) have favorable outcomes, according to study findings published in Journal of the American Academy of Dermatology.

Researchers conducted a retrospective study using a multi-institutional clinical registry and manual cirAE phenotyping. Data were obtained from the Research Patient Data Registry and Enterprise Data Warehouse clinical databases within the Mass General Brigham Health Care System. Patients with cancer who received an ICI from December 1, 2011, to October 30, 2020, were eligible for inclusion.

Researchers conducted landmark survival analyses and time-varying Cox proportional hazards regression modeling with adjustments for age, sex, race or ethnicity, Charlson Comorbidity Index (CCI), ICI type, cancer type, and year of ICI initiation.

A total of 3731 ICI recipients were identified, of whom 676 had a cirAE and 3055 did not have a cirAE. No significant differences were observed in median age at ICI initiation (65.1 vs 65.4 years), mean CCI score (3.30 vs 3.64), and sex (42.9% vs 46.0% women) between the cirAE and noncirAE groups, respectively. The cirAE group had a longer follow-up (913 vs 385 days), higher proportion of White patients (93.8% vs 90.4%), and a higher proportion of those with melanoma (35.7% vs 17.1%), compared with the noncirAE group, respectively.

We find cirAEs to be associated with increased survival as a group and additionally, significantly improved prognosis is observed among other morphologies in addition to vitiligo.

According to multivariate time-varying Cox proportional hazards models, having cirAEs was significantly associated with better survival in analysis of all cancer indications (hazard ratio [HR], 0.87; P =.027). Participants who had gastrointestinal malignancies (HR, 1.32; P <.001) had worse outcomes compared with those with thoracic cancer, and participants with melanoma (HR, 0.44; P <.001) and genitourinary cancer (HR, 0.79; P =.002) had better survival, independent of cirAE development. Those who had a cirAE survived an average of 320 days longer vs those who did not have a cirAE.

Multivariate time-varying Cox proportional hazards analysis was conducted, which limited participants to those who had a specific malignancy. The association of cirAEs with a good prognosis was the strongest in patients with melanoma (HR, 0.67; P =.003).

Sensitivity analyses were performed at 3, 9, and 12 months as alternative landmark times, with 6 months used in the primary model. Patients with cirAEs had a significant survival advantage at 3 months (HR, 0.75; P <.001) and 6 months (HR, 0.83; P =.006), with improved survival at 9 months (HR, 0.89; P =.11) and 12 months (HR, 0.94; P =.5).

Nearly all morphologies were associated with better survival compared with the noncirAE group. Rash (HR, 0.68; P <.001), lichenoid eruption (HR, 0.51; P <.001), psoriasiform eruption (HR, 0.52; P =.005), and others remained significantly associated with improved survival after correction.

Limitations of the study include the retrospective design, and the enrollment of participants from 2 tertiary care cancer centers.

Researchers conclude, “We find cirAEs to be associated with increased survival as a group and additionally, significantly improved prognosis is observed among other morphologies in addition to vitiligo. Together, this suggests that cirAE development after ICI is a key prognostic indicator of survival. This is important in guiding oncologists and dermatologists in managing cirAEs and counseling patients about the prognostic implications of these toxicities.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Zhang S, Tang K, Wan G, et al. Cutaneous immune-related adverse events are associated with longer overall survival in advanced cancer patients on immune checkpoint inhibitors: a multi-institutional cohort study. J Am Acad Dermatol. Published online January 31, 2023. doi:10.1016/j.jaad.2022.12.048