Beyond corticosteroids for the management of patients with cutaneous immune-related adverse events secondary to immune checkpoint inhibitors
Published Date: 01st September 2020
Publication Authors: Hindle E
Abstract
Immune checkpoint inhibitors (ICIs) restore antitumour immunity and have revolutionized the treatment of several types of malignancy, including melanoma. However, these immunotherapeutic agents are often associated with immune‐related adverse events (irAEs), most commonly in the skin. Guidelines from the European Society for Medical Oncology recommend the use of corticosteroids for treatment of cutaneous irAEs (Haanen J, Carbonnel F, Robert C et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines. Ann Oncol 2017; 28: iv119–42). However, some patients require large doses or recurrent courses of corticosteroids leading to side‐effects and delay or withdrawal of ICI therapy. There is a need for alternative treatments for cutaneous irAEs. From January 2019 to January 2020 all cases of ICI‐induced cutaneous irAEs referred to a specialist dermatology unit were reviewed to identify patients who required systemic immunosuppression with medication other than corticosteroids. Demographics, clinical features, investigations and outcomes for patients were recorded. Five patients were treated with mycophenolate mofetil (MMF) and a single patient with methotrexate for cutaneous irAEs. All six patients were male and their primary malignancies were metastatic melanoma. Three patients were commenced on combination immunotherapy (ipilimumab and nivolumab), with the remaining patients on pembrolizumab alone. One patient on combination therapy developed a severe bullous exfoliative dermatitis requiring intravenous corticosteroids and MMF. His cutaneous toxicity resolved, but he developed sepsis secondary to an infected humeral prosthesis. Two patients receiving combination ICI and a single patient on pembrolizumab presented with recurrent lichenoid eruptions requiring multiple courses of oral corticosteroids. MMF was prescribed in these cases resulting in improvement in cutaneous toxicity, cessation of oral corticosteroids and continuation of ICI therapy. One patient receiving pembrolizumab required MMF for control of a severe flare of pre‐existing atopic dermatitis, which was poorly responsive to corticosteroids. The final patient had to restart methotrexate, which was initially stopped at the diagnosis of melanoma, for flare of chronic actinic dermatitis secondary to pembrolizumab. Systemic immunosuppression with MMF and methotrexate were effective in our cohort for the management of severe cutaneous irAEs that were unresponsive to or required long‐term corticosteroids. Existing studies have not identified differences in overall outcomes for patients who received immunosuppression vs. patients who did not require immunosuppressive agents for irAEs during ICI therapy (Horvat TZ, Adel NG, Dang TO et al. Immune‐related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Centre. J Clin Oncol 2015; 33: 3193–8). MMF is already recommended for the management of hepatitis, pneumotoxicity and cardiac toxicity secondary to ICIs (Haanen et al.). Further studies are required to explore the relationships between immunosuppression (e.g. type, timing, duration) and clinical outcomes for patients prescribed ICIs.
Yip, V; Olsson-Brown, A; Carr, D; Pirmohamed, M; Hindle, E. (2020). Beyond corticosteroids for the management of patients with cutaneous immune-related adverse events secondary to immune checkpoint inhibitors. British Journal of Dermatology. 183 (S1), 136