Abstract
Background
Ipilimumab is an immunomodulatory antibody directed against cytotoxicT-lymphocyte-associated antigen 4 (CTLA-4), which is administered to patients with advanced melanoma, with a proven positive effect on overall survival. The cutaneous adverse effects (AEs) of ipilimumab are relatively frequent, although described as usually mild and rarely life threatening.
Objectives
To describe a three-year experience of a single institute in detecting and managing cutaneous AEs.
Materials & Methods
A cohort of patients (n = 41) treated with ipilimumab (3 mg/kg/three weeks) for metastatic melanoma, from 2013 to 2016,was investigated for adverse cutaneous events.
Results
On dermatological evaluation, 34.1% of the patients in our series developed cutaneous AEs: rash (7.3%; n = 3), folliculitis (7.3%; n = 3), mucositis (2.4%; n = 1), rosacea (2.4%; n = 1), eczema (2.4%; n = 1), acneiform eruption (2.4%; n = 1), syringometaplasia mucinosa (2.4%; n = 1), Stevens-Johnson syndrome (2.4%; n = 1), and vitiligo (4.9%; n = 2). These were all Grade 1 and 2 AEs, except for the case of Stevens-Johnson syndrome (Grade 4). On a patient-reported scale, 4.9% (n = 2) and 9.8% (n = 4) of the patients complained of severe xerosis and pruritus, respectively.
Conclusion
Ipilimumab was relatively well tolerated in our series, mainly causing mild cutaneous AEs, which, in our experience, responded satisfactorily to conventional therapies. Only in one case was the treatment discontinued, due to Grade 4 side effects.
Similar content being viewed by others
References
Naidoo J, Page DB, Li BT, et al. Toxicities of the anti-PD-1 andanti-PD-L1 immune checkpoint antibodies. Ann Oncol 2015; 26: 2375.
Champiat S, Lambotte O, Barreau E, et al. Management of immunecheckpoint blockade dysimmune toxicities: a collaborative positionpaper. Ann Oncol 2016; 27: 559.
Chen AP, Setser A, Anadkat MJ, et al. Grading dermatologicadverse events of cancer treatments: The Common Terminology Criteriafor Adverse Events Version 4.0. J Am Acad Dermatol 2012; 67: 1025–39.
Williamson A, Hoggart B. Pain: a review of three commonly usedpain rating scales. J Clin Nurs 2005; 14: 798–804.
Hofmann L, Forschner A, Loquai C, et al. Cutaneous, gastrointestinal,hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. EurJ Cancer 2016; 60: 190e209.
Weber JS, Kähler KC, Hauschild A. Management of immune-relatedadverse events and kinetics of response with ipilimumab. J Clin Oncol 2012; 30: 2691.
Lacouture ME, Wolchok JD, Yosipovitch G, et al. Ipilimumab inpatients with cancer and the management of dermatologic adverseevents. J Am Acad Dermatol 2014; 71: 161.
Minkis K, Garden BC, Wu S, Pulitzer MP, Lacouture ME. The riskof rash associated with ipilimumab in patients with cancer: a systematicreview of the literature and meta-analysis. J Am Acad Dermatol 2013; 69: e121–8.
Spain L, Diem S, Larkin J. Management of toxicities of immunecheckpoint inhibitors. Cancer Treat Rev 2016; 44: 51–60.
Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combinednivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373: 23–34.
Ludlow SP, Kay N. Delayed dermatologic hypersensitivity reactionsecondary to ipilimumab. J Immunother 2015; 38: 165–6.
Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumabin advanced melanoma. N Engl J Med 2015; 372: 2521–32.
Robert C, Long GV, Brady B, et al. Nivolumab in previouslyuntreated melanoma without BRAF mutation. N Engl J Med 2015; 372: 320–30.
Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versuschemotherapy in patients with advanced melanoma who progressedafter anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled,open-label, phase 3 trial. Lancet Oncol 2015; 16: 375–84.
Hua C, Boussemart L, Mateus C, et al. Association of vitiligowith tumor response in patients with metastatic melanoma treated withpembrolizumab. JAMA Dermatol 2016; 152: 45–51.
Klein O, Ebert LM, Nicholaou T, et al. Melan-A-specific cytotoxic Tcells are associated with tumor regression and autoimmunity followingtreatment with anti-CTLA-4. Clin Cancer Res 2009; 15: 2507–13.
Pintova S, Sidhu H, Friedlander PA, Holcombe RF. Sweet’s syndromein a patient with metastatic melanoma after ipilimumab therapy. Melanoma Res 2013; 23: 498.
Abdel-Rahman O, ElHalawani H, Fouad M. Risk of cutaneoustoxicities in patients with solid tumors treated with immune checkpointinhibitors: a meta-analysis. Future Oncol 2015; 11: 2471–84.
Dick J, Lang N, Slynko A, et al. Use of LDH and autoimmune sideeffects to predict response to ipilimumab treatment. Immunotherapy 2016; 8: 1033–44.
Author information
Authors and Affiliations
Corresponding author
Additional information
To cite this article: Dika E, Ravaioli GM, Fanti PA, Piraccini BM, Lambertini M, Chessa MA, Baraldi C, Ribero S, Andrea A, Melotti B, Patrizi A. Cutaneous adverse effects during ipilimumab treatment for metastatic melanoma: a prospective study. Eur J Dermatol 2017; 27(3): 266-70 doi:10.1684/ejd.2017.3023
About this article
Cite this article
Dika, E., Ravaioli, G.M., Fanti, P.A. et al. Cutaneous adverse effects during ipilimumab treatment for metastatic melanoma: a prospective study. Eur J Dermatol 27, 266–270 (2017). https://doi.org/10.1684/ejd.2017.3023
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1684/ejd.2017.3023