Cutaneous adverse effects of the immune checkpoint inhibitors |
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Institution: | 1. Section of Dermatology, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire;2. Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire;1. Department of Medicine, Mayo Clinic, Jacksonville, Florida;2. Department of Medicine, Mayo Clinic, Rochester, Minnesota;1. Division of Medical Oncology, National Cancer Centre, Singapore;2. Department of Dermatology, Singapore General Hospital, Singapore;1. Department of Dermatology, Central Utah Clinic, Provo, Utah;2. Department of Pathology, Central Utah Clinic, Provo, Utah;3. Macdonald Graphic Design, Inc, Provo, Utah;4. Department of Dermatology, University of Colorado-Denver, Aurora, Colorado;5. Department of Pathology, University of Colorado-Denver, Aurora, Colorado;6. Department of Oncology, Wayne State University, Detroit, Michigan;7. Department of Dermatology, Mayo Clinic, Scottsdale, Arizona;1. Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Germany;2. Department of Dermatology, University Hospital Heidelberg, Germany;3. Department of Dermatology and Allergy, University Hospital Munich, Munich, Germany;4. Department of Internal Medicine III, University Hospital Hamburg Eppendorf, Germany;5. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany;6. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Germany;7. Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Germany;8. Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany;9. Department of Thoracic Oncology, LungenClinic Grosshansdorf, Germany;10. Department of Thoracic Oncology, Thoraxklinik, University of Heidelberg, Germany;11. Department of Dermatology, University Hospital, University Essen-Duisburg, Germany;12. Bristol-Myers Squibb GmbH&KGaA, Munich, Germany;13. Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany;1. Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA;2. Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA;3. Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA;4. Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA;5. Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA;6. Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA;7. Division of Medical Oncology, Department of Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA;8. Pathology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA;9. College of Medicine and Life Sciences, University of Toledo, Health Science Campus, 3000 Arlington Avenue, Toledo, OH, USA;10. Weill Cornell Medical College, New York, NY, USA;11. Division of Hematology and Oncology, Department of Medicine, Northport VA Medical Center, Northport, NY, USA |
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Abstract: | The immune checkpoint targeted agents, anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and anti–programed cell death 1 (PD-1) or anti–programmed death ligand 1 (PD-L1) inhibitors are frequently associated with cutaneous side effects that are often dose limiting and can lead to discontinuation of therapy. Ipilimumab, a CTLA-4 inhibitor, is most commonly associated with a morbilliform eruption on the trunk and extremities and pruritus. More severe cutaneous toxicities reported include toxic epidermal necrolysis and severe drug rash with eosinophila and systemic symptoms. Recent case reports of Sweet syndrome and cutaneous sarcoidosis have also recently been described after treatment with ipilimumab. The cutaneous events usually occur early in the course of treatment and are dose dependent. PD-1 inhibitors, nivolumab and pembrolizumab, induce similar but less severe toxicities compared with the CTLA-4 inhibitors. The most common cutaneous adverse events include lichenoid reactions, eczema, vitiligo, and pruritus. Lichenoid oral mucosal lesions located on the tongue, buccal mucosa, lips, or gingivae or located on all of these have also recently been described. The time of onset of the cutaneous events with the PD-1 inhibitors occurs later than that seen with the CTLA-4 inhibitors. Anti–PD-L1 antibodies, such as atezolizumab, have a similar side effect profile compared with the PD-1 inhibitors. Combination of immune checkpoint inhibitors, ipilimumab and nivolumab, has recently been approved for the treatment of advanced melanoma. The combination therapy is associated with a more severe side effect profile compared with the agents used as monotherapy. We discuss the most frequently encountered cutaneous side effects of the immune checkpoint inhibitors and review the recommended management strategies. |
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Keywords: | Immune checkpoint inhibitors Cutaneous adverse effects PD-1 inhibitors CTLA-4 inhibitors Melanoma |
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