Immune-Related Adverse Events: Advances in the Management of Immunotherapy Treatments

Immune-Related Adverse Events: Advances in the Management of Immunotherapy Treatments


Laura S. Wood

By Laura S. Wood, RN, MSN, OCN

Article Highlights

  • Key components for successful management of irAEs include education, awareness, communication, collaboration, and multidisciplinary care.
  • IrAEs generally occur in the first 6 months, although delayed onset has been observed with all immunotherapy agents.
  • Existing algorithms and publications emphasize the benefit and necessity of a multispecialty approach to the management of irAEs.

Treatment options in oncology are expanding at a rapid pace, and advances in translational and clinical research offer new hope for patients with cancer. Identification and management of treatment-related adverse effects is crucial to provide patients with the opportunity to achieve maximal benefits from therapy. As experience with immunotherapy broadens and more drugs are approved for an increasing number of malignancies, the need for oncology providers to gain knowledge about the types and management of immune-related adverse events (irAEs) becomes increasingly important. Providers must understand the differences in immunotherapies, their mechanisms of action, and the variability of irAEs.

Key components for successful management of irAEs include education, awareness, communication, collaboration, and multidisciplinary care. Most patients will experience mild and/or intermittent adverse effects, but some will experience severe and potentially life-threatening, distinct adverse effects that result from the nonspecific activation of the immune system by checkpoint inhibitors. These adverse events occur as a consequence of impaired self-tolerance from loss of T-cell inhibition and can involve every organ system.1

Professional education and awareness of publications about immunotherapy are essential, because the spectrum of irAEs differs between agents and will differ when the same immunotherapy is used in different malignancies. Providers must recognize that CTLA-4 and PD-1 regulate immune responses at different levels and by different mechanisms.2 CTLA-4 primarily regulates T-cell activation in the lymphoid organs; PD-1 is a negative regulator of T-cell activity within the peripheral tissues and the tumor microenvironment.3 Knowledge of the diversity of irAEs is the first step in proactive care for patients who receive immunotherapy. Infusion nurses must be educated about irAEs, too, because they may be the practitioner who identifies these adverse events. They also play a critical role in educating patients and loved ones about the development of potential irAEs; patient awareness allows for early assessment and intervention.

Treatment and Management of IrAEs

IrAEs generally occur in the first 6 months of therapy, although delayed onset has been observed with all immunotherapy agents. Overlapping toxicities when these drugs are combined with other therapeutic strategies challenge clinicians to determine the etiology of symptoms. It is essential to exclude other etiologies because the interventions for irAEs are specialized. Various algorithms for the management of irAEs have been developed and provide a framework for oncology providers.4-6

Use of existing algorithms can guide treatment of irAEs. Once an adverse event is determined to be immune related, treatment interruption is the first intervention, which emphasizes the importance of communication within the oncology care team. Continued management includes consideration of topical corticosteroids for dermatologic irAEs and systemic corticosteroids for others. Symptoms that persist despite systemic corticosteroids or worsen when corticosteroids are tapered may respond to immunomodulatory or immunosuppressive agents, such as TNF-alpha antagonists.

Existing algorithms and publications emphasize the benefit and necessity of a multispecialty approach to irAE management. Comprehensive care expands upon the five pillars of immunotherapy toxicity management published by Champiat et al,4 which I have modified—by changing prevent to educate and detect to assess—to demonstrate a more active and ongoing process. I also have expanded the model to include “evaluate” and “collaborate,” because these adverse events may continue for extended periods of time, may affect decisions about subsequent treatment, and may require multidisciplinary management (Fig. 1). Many cancer centers have developed multidisciplinary tumor boards or clinics to improve collaboration and to develop algorithms that streamline diagnostic workup and treatment strategies. A recent supplement issue to the Clinical Journal of Oncology Nursing focused on the treatment of melanoma and the assessment and management of irAEs.7-10 Prompt recognition and optimal management of irAEs are essential requirements to maximize clinical outcomes.11

Conferences such as the ASCO-SITC Clinical Immuno-Oncology Symposium provide an opportunity to network and share best practices. Organizations such as the Oncology Nursing Society, National Comprehensive Cancer Network, ASCO, SITC, Association of Community Cancer Centers, and others are collaborating to improve our understanding and expand our expertise in the care of patients who receive immunotherapy. I encourage you to share articles with your colleagues, clinical staff, and infusion nurses because there is much to be learned from sharing expert resources. Please take copies of the ASCO-SITC Clinical Immuno-Oncology Symposium Daily News to your colleagues and provide them easy access to information shared at this conference.

About the Author: Ms. Wood is the Renal Cancer Research Coordinator with the Cleveland Clinic Taussig Cancer Center.