Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti‐CTLA4 and anti‐PD1 combination immunotherapy: Incidence, management, and clinical benefit. Issue 5 (1st November 2021)

• Record Type: Journal Article
• Authors: Patel, Anisha B.; Farooq, Sahira; Welborn, Macartney; Amaria, Rodabe N.; Chon, Susan Y.; Diab, Adi; Glitza Oliva, Isabella C.; Huen, Auris O.; Li, Shirley Q.; Nelson, Kelly C.; Pacha, Omar; Patel, Sapna P.; Rapini, Ronald P.; Tawbi, Hussein A.; Wong, Michael K.; McQuade, Jennifer; Davies, Michael A.; Haydu, Lauren E.
• Is Part Of: Cancer. Volume 128:Issue 5(2022)
• Page Start: 975
• Page End: 983
• Publication Date: 2021-11-01
• Subjects: anti–cytotoxic T‐lymphocyte–associated antigen 4 (anti‐CTLA4) -- anti–programmed death 1 (anti‐PD1) -- cutaneous adverse events -- immune checkpoint inhibitors -- ipilimumab -- melanoma -- nivolumab -- pembrolizumab; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.34004
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : Background: In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. Methods: Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time‐dependent Cox regression to identify associations with TTNT. Results: Eighty‐one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0‐341 days) and 50 days (range, 1‐352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune‐related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331‐0.972; P = .039). Conclusions: CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit. Abstract : Cutaneous adverse events (CAEs) in patients with melanoma treated with combination checkpoint inhibitor therapy are mostly reversible and rarely require therapy discontinuation. The development of CAEs is associated with a longer time to the next treatment, and this suggests a possible clinical benefit.