Ipilimumab in patients with cancer and the management of dermatologic adverse events - 18/06/14

Doi : 10.1016/j.jaad.2014.02.035

Mario E. Lacouture, MD ^a,^b,^⁎ , Jedd D. Wolchok, MD, PhD ^a,^b,^c, Gil Yosipovitch, MD ^d, Katharina C. Kähler, MD ^e, Klaus J. Busam, MD ^a, Axel Hauschild, MD ^e
^a Memorial Sloan Kettering Cancer Center, New York, New York
^b Weill-Cornell Medical College, New York, New York
^c Ludwig Institute for Cancer Research, New York, New York
^d Departments of Dermatology, Neurobiology and Anatomy, and Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina
^e Department of Dermatology, University of Kiel, Kiel, Germany

^∗Correspondence to: Mario E. Lacouture, MD, Memorial Sloan Kettering Cancer Center, Suite 228, 160 E 53 St, New York, NY 10022.

Abstract

Ipilimumab is a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to augment antitumor T-cell responses. Phase III studies have demonstrated survival benefit in both previously treated and treatment-naïve patients with metastatic melanoma. In clinical trials, adverse events (AEs) related to treatment with ipilimumab were mostly grade 1/2 (as per Common Terminology Criteria for AEs, Version 4.02), and mostly reversible with appropriate management. Distinct immune-related AEs that may reflect the mechanism of action of ipilimumab have been identified, and occur commonly in the skin, typically presenting as a maculopapular rash, which can be accompanied by pruritus, pruritus with no skin lesions, alopecia, and vitiligo. Histologic analyses have revealed epidermal spongiosis, and perivascular CD4⁺ T-cell infiltrates with some eosinophils in areas of rash. Timely implementation of toxicity-specific treatment guidelines that emphasize vigilance and early intervention allows mitigation of dermatologic AEs. Adherence to guidelines is necessary to maintain quality of life, ensure consistent dosing, and obtain the best possible clinical outcome.

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Key words : adverse event management, dermatologic, immune-related, ipilimumab, melanoma, pruritus, rash, vitiligo

Abbreviations used : AE, CTLA, GI, irAE

Plan

Ipilimumab mechanism of action

Ipilimumab efficacy in metastatic melanoma

Safety overview

Skin AEs

Incidence of skin AEs

Pruritus

Rash

Severe (grade ≥3) skin irAEs

Typical features of ipilimumab-induced cutaneous AEs

Appearance

Histology

Time to onset of irAEs

Grading and management of skin irAEs

Evidence

Guidance

Conclusions

	The authors take full responsibility for the content of this publication and confirm that it reflects their viewpoint and medical expertise. The authors also wish to acknowledge StemScientific, funded by Bristol-Myers Squibb, for providing writing and editorial support. Neither Bristol-Myers Squibb nor StemScientific influenced the content of the manuscript, nor did the authors receive financial compensation for authoring the manuscript.
	Disclosure: Dr Lacouture received honoraria for advisory board membership and consultancy with Bristol-Myers Squibb and consultancy for Advancell, Amgen, Bayer, Berg, Galderma, Genentech, GSK, Helsinn, Merck, Novartis, Novocure, OSI, and Pfizer. Dr Wolchok received honoraria for consultancy for AstraZeneca, Bristol-Myers Squibb, and Merck. Dr Kähler received honoraria for advisory board membership, consultancy, and as a speaker. Dr Hauschild received honoraria for advisory board membership and consultancy as well as payments for lectures including services on speakers' bureaus and research funding from the following companies: Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eisai, GSK, IGEA, Lilly, MelaSciences, Merck Serono, MSD/Merck, Novartis, Oncosec, and Roche Pharma. Drs Yosipovitch and Busam have no conflicts of interest to declare.
	Reprints not available from the authors.