Comparative severe dermatologic toxicities of immune checkpoint inhibitors in malignant melanoma: A systematic review and network meta-analysis.

Publisher: Blackwell Science Country of Publication: England NLM ID: 101130964 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1473-2165 (Electronic) Linking ISSN: 14732130 NLM ISO Abbreviation: J Cosmet Dermatol

Original Publication: Oxford, UK : Blackwell Science, c2002-

Immune Checkpoint Inhibitors*/adverse effects ; Ipilimumab*/adverse effects ; Ipilimumab*/administration & dosage ; Melanoma*/drug therapy ; Network Meta-Analysis* ; Nivolumab*/adverse effects ; Nivolumab*/administration & dosage ; Skin Neoplasms*/drug therapy; Humans ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Drug Eruptions/diagnosis ; Drug Eruptions/etiology ; Randomized Controlled Trials as Topic ; Severity of Illness Index

Background: Immune checkpoint inhibitors (ICIs) have advanced the therapeutic landscape for malignant melanoma patients. However, they can cause permanent and irreversible dermatologic immune-related adverse events (irAEs) that may lead to interruption of ICI treatment or become life-threatening. To assess the risk of severe dermatologic irAEs (grade 3 or higher) among ICIs for advanced melanoma, we conducted a network meta-analysis (NMA).
Methods: Phase II/III randomized controlled clinical trials (RCTs) involving ICIs were retrieved from various databases, including PubMed, Embase, Cochrane Library, and Web of Science. These trials were published from the inception of databases to October 15, 2022. In addition, the risk of severe dermatologic irAEs associated with ICI types and doses was evaluated and compared by NMA.
Results: This study included 20 Phase II/III RCTs with a total of 10 575 patients. The results indicated that ICIs carry a higher risk of severe dermatologic irAEs compared to chemotherapy. Additionally, the combinational therapy of Nivolumab + Ipilimumab was associated with a higher risk than ICI monotherapy. Comparatively, the latest treatment option involving dual ICI therapy with Relatlimab + Nivolumab showed a lower toxicity risk, but higher than Ipilimumab alone. Lastly, Nivolumab, at a dose of 3 mg/kg every 2 weeks, was observed as the lowest-risk dosing regimen for severe dermatologic irAEs in patients with advanced melanoma.
Conclusion: The findings suggest that Nivolumab (1 mg/kg) + Ipilimumab (3 mg/kg) administered every 3 weeks should be used cautiously in patients with advanced melanoma at high risk for dermatologic irAEs. While we recommend the preferred regimen of Nivolumab (dose = 3 mg/kg, every 2 weeks).
(© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

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81971864 National Natural Science Foundation of China

Keywords: dermatologic toxicities; immune checkpoint inhibitors; immunotherapy; melanoma; meta‐analysis

0 (Immune Checkpoint Inhibitors)
0 (Ipilimumab)
31YO63LBSN (Nivolumab)

Date Created: 20231128 Date Completed: 20240807 Latest Revision: 20240809

20250114

10.1111/jocd.16105

38013634