A number of immune checkpoint inhibitors (ICIs) have been approved by the U.S. Food and Drug Administration (FDA) as immuno-oncology (IO) monotherapy for multiple solid and hematologic tumor types across various lines of therapy. Furthermore, evidence shows some patients may derive additional benefit from IO combination therapy. Three IO combination regimens, nivolumab plus ipilimumab, and pembrolizumab or atezolizumab plus chemotherapy, are approved by the FDA as of April 2019. Because peripheral immune surveillance via T-cell activity is increased to attack malignant cells, the antitumor effects of ICIs may be accompanied by immune-mediated adverse reactions (IMARs). Although potentially more efficacious than monotherapy, IO combination therapies are associated with increased incidences of IMARs vs. IO monotherapy. Advanced practice providers (APPs) are uniquely placed within the multidisciplinary team to counsel patients with cancer on their IO treatment and educate them about identifying manifestations of IMARs. Advanced practice providers should be aware of the presentation and time to onset of IMARs, appropriate management to reduce risk of organ dysfunction, and guidelines for treating these patients. This article reviews IO/IO and IO/chemotherapy combination regimens with respect to clinical efficacy and safety, and discusses the role of the APP in managing IMARs associated with IO combination therapy.
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