Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor
Open accessAbstract
Background Dermatologic adverse events (AEs) are some of the most frequently observed toxicities of immune-checkpoint inhibitor therapy, but have received little attention. The drugs, pembrolizumab and nivolumab are recently approved inhibitors of the PD-1 receptor that have overlapping AE profiles however, the incidence, relative risk (RR), and clinico-morphological pattern of the associated dermatologic AEs is not known. Methods We conducted a systematic review of the literature, and performed a meta-analysis of dermatologic AEs with the use of pembrolizumab and nivolumab in cancer patients. An electronic search was conducted using the PubMed, and Web of Science, and on the ASCO and ESMO meeting abstracts’ library for potentially relevant oncology trials employing the drugs at FDA-approved doses and reporting dermatologic AEs. The incidence, relative risk and 95% CIs were calculated using either random- or fixed-effects models based on the heterogeneity of included studies. The clinical presentation, histology of affected areas, and management strategies based on institutional experience, are also presented. Results Rash, pruritus and vitiligo were the most frequently reported AEs. The calculated incidence of all-grade rash with pembrolizumab and nivolumab was 16.7% (RR=2.6) and 14.3% (RR=2.5), respectively. Other significant all-grade AEs included pruritus [pembrolizumab: incidence, 20.2% (RR=49.9); nivolumab: incidence, 13.2% (RR=34.5)] and vitiligo [pembrolizumab: incidence, 8.3% (RR=17.5); nivolumab: 7.5% (RR=14.6)]. Interestingly, all the vitiligo events were reported in trials investigating melanoma. The RR for developing dermatologic toxicities in general, was 2.95 with pembrolizumab, and 2.3 with nivolumab. Conclusion We found that pembrolizumab and nivolumab are both associated with dermatologic AEs, primarily low-grade rash, pruritus, and vitiligo, which are reminiscent of those seen with ipilimumab. Knowledge of these findings is critical for optimal care, maintaining dose intensity, and health-related quality of life, in cancer patients receiving PD-1 inhibitors.
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Corticosteroids are the usual first-line treatment for both reactive eosinophilic disorders and irAEs.
“Corticosteroids are the usual first-line treatment for both reactive eosinophilic disorders and irAEs.2,7,23”
From Moderate-to-severe eosinophilia induced by treatment with immune checkpoint inhibitors: 37 cases from a national reference center for hypereosinophilic syndromes and the French pharmacovigilance database (2020) · cites this paper as [23]
The Results (Case Series) and Discussion report that topical corticosteroids generally sufficed for PD-1 inhibitor–associated rashes, with oral corticosteroids sometimes needed. This supports corticosteroid treatment for dermatologic irAEs, but the paper does not address first-line treatment of reactive eosinophilic disorders or irAEs generally. Page numbers were not provided in our copy. (LLM, conf=0.86)
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“reactive eosinophilic disorders and irAEs.(2,7,23) Our results suggest that corticosteroids constitute an effective treatment for moderate-to-severe eosinophilia, even though the dosage was not specified in the pharmacovigilance reports.”
- Authors
- Belum, V. R., Benhuri, B., Postow, M. A., Hellmann, M. D., Lesokhin, A. M., Segal, N. H., Motzer, R. J., Wu, S., Busam, K. J., Wolchok, J. D., & Lacouture, M. E.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- State University of New York (US)
- Corresponding author
- Lacouture, M.E.
- ORCID
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 60
- Pages
- 12-25
- ISSN
- 0959-8049 (ISSN-L)
- PMC
- PMC4998047
- OpenAlex
- W2329871425
- Semantic Scholar
- 2299e9c917547fea8532a36fe748bbb31203fa3c
- Cited by
- 418
- References
- 48
- Citations by year
- 2026: 26 · 2025: 23 · 2024: 29 · 2023: 40 · 2022: 43 · 2021: 58 · 2020: 63 · 2019: 43 · 2018: 39 · 2017: 39 · 2016: 15
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- European Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30 CA008748)
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Dermatology › Chemotherapy-related skin toxicity
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Keywords
- dermatologic adverse events, immune checkpoint inhibitors, PD-1 receptor, pembrolizumab, nivolumab, rash, pruritus, vitiligo, melanoma, adverse event incidence, relative risk, adverse event management, ipilimumab, cancer immunotherapy toxicity
- MeSH terms
- Nivolumab, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Clinical Trials as Topic, Drug Eruptions, Exanthema, Female, Humans, Male, Middle Aged, Neoplasms, Pruritus, Vitiligo, Young Adult, Cell Cycle Checkpoints, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized
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