Kahler, K.C., Hassel, J.C., Heinzerling, L., Loquai, C., Mossner, R., Ugurel, S., . . . \"Cutaneous Side Effects\" Committee of the Work Group Dermatological Oncology (ADO). (2016). Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti-PD-1 antibodies in metastatic melanoma. Journal of the German Society of Dermatology, 14, 662–681.

RESOURCE TYPE: Expert opinion  

PROCESS OF DEVELOPMENT: Clinical review

This article provides an overview of the mechanisms of action of immune checkpoint blockade and clinical effects in metastatic melanoma. The focus is the adverse effect profile and therapeutic management. The side effect profile includes a review of a meta-analysis of 1,265 patients from 22 clinical trials who received ipilimumab. Eighty-two to ninety-five percent of patients experienced treatment-related side effects. Incidence tables are provided as well as a checklist for important questions during patient visits, blood test recommendations, and organ-specific side effects. Diarrhea and colitis are described with a table of trade, treatment, and follow-up. Other organ-specific side effects are also reviewed. Recommendations for management algorithms are discussed.

Comprehensive clinical studies have shown a major benefit of anti-CTLA-4 antibody ipilimumab and two anti-PD-1 antibodies nivolumab and pembrolizumab in various tumors, including melanoma. These agents enhance an autoimmune phenomenon that affects various organs. Persistent diarrhea and colitis are evidenced early in treatment and can be serious adverse effects. The clinical significance is the debilitating effect they have on patients, with electrolyte disturbances and protracted weight loss. Intestinal perforation is a serious risk. Grade 1–2 diarrhea is treated with loperamide and electrolyte replacement. An endoscopy should be considered with persistent low-grade diarrhea because it diagnoses the true extent of the colitis. For grade 3–4 diarrhea/colitis, immunotherapy should be discontinued and high-dose corticosteroids initiated. Symptoms improve markedly with this regimen. Treatment with infliximab (5 mg/kg) is used in rare cases in which steroids do not induce a response. Colitis is associated with ocular inflammation, and observing for this side effect is imperative. Comprehensive study data identify that the timely and consistent use of corticosteroids allows for control and regression of symptoms in the majority of cases.

This is an overview of a complex multidisciplinary side-effect management concern with new checkpoint inhibitors. Further study would be necessary for a nurse to acquire in-depth knowledge for patient care.

Immuno-oncology is becoming a mainstay of pharmacological cancer treatment. Knowledge of side effects of these checkpoint inhibitors, especially diarrhea and colitis, is essential to their prevention, treatment, and management. Early recognition and intervention can reduce sequelae for patients.