Treatment of Immune Checkpoint Inhibitor Immune-Related Cutaneous Adverse Events
In a study reported in the Journal of Clinical Oncology, Phillips et al found that immune-related cutaneous adverse events in patients receiving immune checkpoint inhibitors generally responded to symptom- and phenotype-directed dermatologic therapies, and that biologic therapies were effective in corticosteroid-refractory adverse events.
Study Details
The study was a retrospective analysis of data from 285 patients with immune-related cutaneous adverse events treated at oncodermatology clinics at Memorial Sloan Kettering Cancer Center, Columbia University Medical Center, and University Federico II between January 2014 and December 2017.
Immune-Related Cutaneous Adverse Event Profiles and Response to Treatment
Patients had 427 immune-related cutaneous adverse events, including pruritus (32%), maculopapular rash (28%), psoriasiform rash (5%), and others (34%). Immune checkpoint inhibitor type was associated with immune-related cutaneous adverse event phenotype (P = .007); for example, maculopapular rash was predominant in patients receiving combination therapy, and bullous pemphigoid-like eruptions were more common in patients receiving anti–programmed cell death protein 1/programmed cell death ligand-1(PD-1/PD-L1) monotherapy than in those receiving anti–CTLA-4 agents with or without anti–PD-1/PD-L1 agents. Most immune-related cutaneous adverse events (87%) were grade 1 to 2 in severity. No association was observed between immune-related cutaneous adverse event severity and immune checkpoint inhibitor type (P = .37).
The severity of immune-related cutaneous adverse events was significantly reduced with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators (mean Common Terminology Criteria for Adverse Events grade = 1.74 vs 0.71, P < .001). Of 88 immune-related cutaneous adverse events (20%) treated with systemic immunomodulators, 22 (25%) persisted or worsened. In seven patients with corticosteroid-refractory immune-related cutaneous adverse events, use of targeted biologic immunomodulatory therapies, including rituximab and dupilumab, resulted in improvement.
Interleukin-6 (IL-6) was elevated in 34 (52%) of 65 evaluated patients. Grade ≥ 3 immune-related cutaneous adverse events were associated with increased absolute eosinophils (odds ratio [OR] = 4.1, 95% confidence interval [CI] = 1.3–13.4) and increased IL-10 (OR = 23.8, 95% CI = 2.1–262.5). Immunoglobulin E levels increased with increasing grade of immune-related cutaneous adverse events (P = .043).
The investigators concluded, “Most [immune-related cutaneous adverse events] responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with [immune-related cutaneous adverse events], and they may represent actionable therapeutic targets for immune-related skin toxicities.”
Mario E. Lacouture, MD, of the Dermatology Service, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by National Cancer Institute grants and by Beca Excelencia Fundacíon Piel Sana. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
