Management of skin adverse events associated with immune checkpoint inhibitors in patients with melanoma: A nursing perspective.

PURPOSE: Immune checkpoint inhibitors are associated with a unique immune-related side effect profile that requires prompt recognition and management. Skin toxicities are the most common, and often earliest occurring, drug-related adverse events (AEs) of any grade observed upon treatment with these agents. The purpose of this review is to provide practical guidance on the identification and treatment of skin AEs associated with the immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab) from a nursing perspective, and demonstrate hands-on application of the guidance using relevant patient case studies. DATA SOURCES: Data for drug-related skin AEs were summarized from phase 3 nivolumab and nivolumab + ipilimumab trials and phase 2 and 3 pembrolizumab trials. Patient case studies were provided by the lead (M.T.) and senior (J.N.C.) authors. CONCLUSIONS: The recommendations presented here, based on accumulated clinical trial and clinical practice experience are consistent with established treatment guidelines and reach beyond established guidelines and recommendations for the management of AEs associated with immune checkpoint inhibitors. IMPLICATIONS FOR PRACTICE: The practical treatment guidance presented here may help familiarize medical teams with the recognition and management of skin AEs associated with these recently approved agents. The enclosed recommendations may contribute to optimized treatment through awareness of typical time to onset and clinical presentation, knowledge of management options, and appropriate application of treatment.

Understanding and Managing Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Patients With Advanced Melanoma.

The immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab represent a substantial improvement in treating advanced melanoma but are associated with adverse events (AEs) likely related to general immunologic enhancement. To ensure that patients receive optimal benefit from these agents, prompt assessment and treatment of AEs are essential. We review the efficacy and safety profiles of these immune checkpoint inhibitors and describe guidelines for managing immune-related AEs. We also present case studies describing the management of toxicities in patients receiving immune checkpoint inhibitor therapy. These cases illustrate the importance of collecting a detailed medical history when administering immunotherapy, as this information is necessary to establish baseline, inform monitoring, and determine the etiology of symptoms. Advanced practice nurses and physician assistants are uniquely positioned to educate patients on the early recognition of AEs and have an important role in establishing appropriate monitoring and open dialogue among services.

Advanced Care Provider and Nursing Approach to Assessment and Management of Immunotherapy-Related Dermatologic Adverse Events.

Advanced care providers (ACPs) and nurses are fundamental players in the assessment and management of immunotherapy-related dermatologic adverse events (irdAE). Pembrolizumab, nivolumab, and ipilimumab are approved for unresectable or metastatic melanoma, metastatic non-small cell lung cancer (pembrolizumab and nivolumab), metastatic head and neck squamous cell carcinoma (pembrolizumab and nivolumab), advanced renal cell carcinoma, and Hodgkin lymphoma (nivolumab). Atezolizumab is approved for urothelial carcinoma. These agents function as immune checkpoint inhibitors, activating T-cell-mediated antitumor immune responses through the inhibition of the programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte antigen 4 (CTLA-4). Immune checkpoint inhibitors have been reported to cause irdAEs, including rash, pruritus, and vitiligo, requiring an interdisciplinary approach to avoid dose reduction or discontinuation of treatment and to maintain quality of life. Advanced care providers and nurses play a critical role in the attribution, grading, and management of these untoward events and must be knowledgeable about their pathophysiology, incidence, assessment, and clinical presentation.

Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1.

Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, immune checkpoint mAbs cause cutaneous immune-related adverse events. Although the most commonly reported cutaneous toxicities are mild, a subset may persist despite therapy and can lead to severe or life-threatening toxicity. Autoimmune blistering disorders are not commonly associated with immune checkpoint mAb therapy. We report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Three patients were identified. Two patients developed BP while receiving the anti-PD-1 mAb nivolumab, and one while receiving the anti-PD-L1 mAb durvalumab. The clinicopathologic features of each patient and rash, and corresponding radiologic findings at the development of the rash and after its treatment, are described. Patients receiving an anti-PD-1/PD-L1 mAb may develop immune-related BP. This may be related to both T-cell- and B-cell-mediated responses. Referral to a dermatologist for accurate diagnosis and management is recommended. Cancer Immunol Res; 4(5); 383-9. ©2016 AACR.