Cutaneous Adverse Events are Mild, Manageable for Immune Checkpoint-Treated Melanoma

Anti-CTLA4 and anti-PD1 combination immune checkpoint inhibitors are commonly used to treat melanoma, but they are associated with immune-related adverse events (AEs), including cutaneous AEs. A retrospective study assessed the effect of cutaneous AEs on anti-CTLA4 and anti-PD1 combination therapy for metastatic melanoma and found that most cutaneous AEs were mild and could be managed with topical steroids and/or oral histamines. The results of the study were published as part of the American Academy of Dermatology Virtual Meeting Experience 2020.

Researchers conducted a chart review on 155 consecutively treated patients from 2012 to 2017, not limited to clinical trials, in their institution’s (University of Texas Health Science Center at Houston) database who received at least one dose of ipilimumab with either nivolumab (146 regimens) or pembrolizumab (11 regimens) for unresectable stage III/IV melanoma.

About half of regimens (n=82; 52.2%) resulted in 93 cutaneous AEs, the most common of which were eczema (26%), morbilliform eruption (23%), vitiligo (12%), and pruritis without rash (9%).

Of the total 157 regimens, 97 (61.7%) resulted in combination therapy being discontinued prior to reaching maintenance phase with anti-PD1 treatment only. Immune-related AEs accounted for 59 (60.8%) treatment discontinuations, the most common of which were gastrointestinal (39.0%; n=23), hepatic (37.3%; n=22), endocrine (11.9%; n=7), and pulmonary (11.9%; n=7) toxicities. Among the 82 regimens that resulted in cutaneous AEs, four (5%) resulted in discontinuation due to the cutaneous AE. Nine regimens (11%) had combination therapy dose delays secondary to cutaneous AEs.

Among all regimens, 13 (8.3%) were discontinued or delayed due to cutaneous AEs. Seven required systemic steroids, and four were managed by topical steroids combined with oral antihistamines. The majority of cutaneous AEs were managed with topical steroids and/or oral histamines and resolved after entering maintenance therapy. Vitiligo was the only cutaneous AE that did not resolve.

“Our database includes a real-life population not limited to clinical trial patients showing an incidence of 52.2% for cutaneous AEs on combination therapy compared [with] 40% to 50% reported in clinical trial literature for monotherapy,” the researchers noted.

The study is limited by its inability to determine the types of cutaneous AEs that were diagnosed and managed outside of their institution; thus, incidences of cutaneous AEs may be higher than what could be reported in this study.

“Physicians and patients will benefit from knowing which adverse effects pose the most risk of negatively impacting course of combination anti-CTLA4 and anti-PD1 therapy for metastatic melanoma. Early management is crucial to limit treatment interruptions and negative impacts on quality of life,” the researchers concluded.

Farooq S, Welborn M, Haydu LE, et al. Cutaneous Toxicities in Combination Immune Checkpoint Inhibitor Therapy for Metastatic Melanoma: Impact on Therapy Course. Presented during the AAD Virtual Meeting Experience 2020, June 12-14, 2020.