Incidence of New Primary Cutaneous Melanoma in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors: A Single-Center Cohort Study

Abstract

Importance: The development of new primary cutaneous melanoma (CM) after starting immune checkpoint inhibitor (ICI) therapy is poorly characterized. Objective: To determine the incidence of new CM in patients treated with ipilimumab, nivolumab, and/or pembrolizumab for metastatic melanoma. Design, Setting, and Participants: Single-center, retrospective, observational cohort study using an institutional database to identify patients diagnosed with melanoma at a tertiary care cancer hospital in New York, New York. Exposures: Ipilimumab, nivolumab, and/or pembrolizumab treatment for metastatic melanoma. Main Outcomes and Measures: Primary outcomes were the incidence proportion, the incidence rate, and the 5-year cause-specific cumulative risk. Results: A total of 2251 patients were included in the study; mean (SD) age at the time of ICI start was 62.8 (14.4) years. The majority were male (63.8%, n = 1437), White (92.7%, n = 2086), and non-Hispanic (92.1%, n = 2073). Forty-two of 2251 patients who received ipilimumab, nivolumab, and/or pembrolizumab were diagnosed with 48 new CMs at a median (range) of 397.5 (39-2409) days after ICI initiation. The median age of affected patients at the time of ICI first dose was 66.5 years. The majority were male (66.7%, n = 28), White (92.9%, n = 39), and non-Hispanic (100.0%, n = 42). There were no differences in age, sex, race, and ethnicity among patients who did and did not develop a new CM. Patients who developed a new CM were more likely to have a family history of melanoma (23.8% vs 16.3%, P =.02). Most new CMs (n = 30, 62.5%) were diagnosed after the last date of ICI administration. Twenty-seven (56.3%) new CMs were in situ and 21 (43.8%) were invasive. Of the invasive CMs with a reported Breslow thickness (n = 20), the median (range) thickness was 0.4 (0.1-8.4) mm. The overall incidence proportion of new CM was 1.9% (95% CI, 1.4%-2.5%) and the incidence rate was 1103 cases per 100000 person-years (95% CI, 815-1492). The 5-year cumulative cause-specific risk of new CM was 4.9% (95% CI, 3.3%-7.4%). Conclusions and Relevance: Patients treated with ICI therapy for metastatic melanoma remain at risk for the development of new CM.. © 2021 American Medical Association. All rights reserved