14052 Cutaneous toxicities in combination immune checkpoint inhibitor therapy for metastatic melanoma: Impact on therapy course

Abstract

Side effects of immune checkpoint inhibitor (ICI) therapy for metastatic melanoma (MM) are primarily immune-related adverse events (irAEs). The irAEs from anti-CTLA4 and anti-PD1 agents commonly affect the skin, GI, liver, and endocrine systems; occurring with higher incidences in combination versus monotherapy. Cutaneous adverse events (CAEs) are the earliest and most frequent irAEs with incidence of 40%-50% in monotherapy. Our retrospective study evaluated 157 treatment regimens in 155 patients with MM who received at least one dose of ipilimumab with either nivolumab (146 regimens) or pembrolizumab (11 regimens). CAEs manifested with 82 (52.2%) regimens and included eczema, morbilliform eruption, vitiligo, and pruritis. Out of the 157 regimens evaluated, 97 (61.7%) had discontinuation of treatment prior to the maintenance (anti-PD1 only) phase. IrAEs accounted for 59 (60.8%) of these discontinuations; however, CAEs contributed to 4 (6.8%) of these. Nine (11.0%) additional regimens had delays in combination dosing due to CAEs. Of the 13 regimens impacted by CAEs, 7 required systemic steroids and 4 were managed by topical steroids combined with oral antihistamines. Our database includes a real-world population not limited to clinical trial patients showing an incidence of 52.2% for CAEs on combination therapy compared with 40%-50% reported in literature for monotherapy. CAEs, however, have low impact on therapy course and are low grade, with management limited to topical and/or oral treatment. Both physicians and patients can benefit from being aware of which side effects pose the most risk of negatively impacting the course of combination ICI therapy for metastatic melanoma.