Lacouture, M.E., Wolchok, J.D., Yosipovitch, G., Kähler, K.C., Busam, K.J., & Hauschild, A. (2014). Ipilimumab in patients with cancer and the management of dermatologic adverse events. Journal of the American Academy of Dermatology, 71, 161–169. 

From pooled analysis, 64.2% of patients experienced an IRAEs of any grade, and 17.8% were severe (grade 3 or 4). Dermatologic IRAEs were the most common (44.9% any grade). Most IRAEs develop within the first 12 weeks (five to nine weeks depending on the dose). Ipilimumab rash differs from that of targeted therapies, with ipilimumab rash more closely resembling maculopapular rash. Pruritus with or without rash and can have major impact on quality of life. Ipilimumab appearance, histology, time to onset of IRAEs, grading, and management of skin IRAEs were reviewed.

Guidelines are developed to aid providers to manage IRAEs by early intervention and vigilance. First, determine the severity of the rash or pruritis. For grade 1 or 2 rash, topical corticosteroids and oral antihistamines may be useful. Resume ipilimumab with resolution of rash or with improvement if systemic steroid dose is 7.5 mg of prednisone or less. If grade 3 rash is present, hold ipilimumab and give oral corticosteroids at 1–2 mg/kg/day of prednisone or equivalent. If symptoms improve, healthcare professionals can re-challenge. If symptoms worsen or are evaluated as grade 4, permanently discontinue ipilimumab. Administer corticosteroids at a grade 3 dose and taper for one month if rash improves. For mild or localized pruritus, use topical corticosteroids and antipruritics. For intermittent intense or widespread pruritus, topical corticosteroids and oral antihistamines are indicated. If pruritus is constant, limiting self-care or sleep, use oral antihistamines and corticosteroids and consider gabapentin, pregabalin, mirtazapine, and aprepitant.

These are expert opinion guidelines developed from pooled trial data of patients with metastatic melanoma and from evaluating other clinical trial results of ipilimumab. Interventions are not developed from randomized, controlled clinical trials. These guidelines do not differentiate disease type or dose-related IRAEs.

Quality of life and optimal therapy for patients receiving these new therapies are dependent on vigilance and early detection for interventions. Patient and healthcare providers need to be instructed to recognize findings for improved outcomes early. Mechanisms for patients to report their experiences should be outlined early.