Nivolumab, a new immunomodulatory drug, a new adverse effect; adrenal crisis

Abstract

Owing to the advancements in medicine, new information is obtained regarding cancer, new antineoplastic agents are developed. Frequent use of these new pharmacological agents emergency physicians to be vigilant about their side effects. We present a case of adrenal crisis in a patient with non-small cell lung cancer (NSCLC), caused by an immunomodulatory drug; nivolumab. While adverse events are related to other immunomodulatory drugs have been reported in literature, our case is the first nivolumab-related adrenal failure to be reported. A patient with lung cancer presented to the emergency room(ER) with nausea and vomiting. Hyponatremia, hyperkalemia, persistent hypoglycemia led to the diagnosis of adrenal crisis. Having direct effect on the immune system, these drugs were claimed to be highly reliable. However, there is no reliable data on the side effect profile of these agents. It should be kept in mind that life-threatening auto-immune reactions may occur.

Immune-related adverse events associated with programmed cell death protein-1 and programmed cell death ligand 1 inhibitors for non-small cell lung cancer: a PRISMA systematic review and meta-analysis

“…Two cases of diabetes were also controlled with insulin therapy. One report described life-threatening adrenal crisis following nivolumab treatment [45].…”

A Very Rare Case of Esophagitis Due to Nivolumab Immunotherapy

“…In phase I human studies, skin (20%), gastrointestinal (15%), and pulmonary (9%) toxicities were observed, while in the phase II studies skin (31%), rash (12%), pruritus (9%), vitiligo (3%), gastrointestinal (11%), and pulmonary (3%) were reported. In general, toxicities with anti-PD-1 antibodies appear to be less common and less severe when compared with anti-CTLA-4 monoclonal antibodies [8,9,10]. Dermatologic toxicity is the most common immune-related adverse event associated with checkpoint inhibitors which is usually seen 3-4 weeks after the initiation of therapy.…”

“…Diarrhea/colitis is the most common gastrointestinal symptom presenting approximately 6-8 weeks after the commencement of therapy. [2,8,9,10,11] Boike et al have previously reported endoscopic and histopathological features of esophagitis related to Nivolumab therapy. [2] They noted marked intraepithelial T-cell lymphocytic infiltrates with dyskeratotic keratinocytes.…”

“…After exclusion of other etiologies, management includes initiation of corticosteroid therapy and cessation of Nivolumab in severe cases. [2,10] Interestingly, involvement of the rest of the gastrointestinal tract is rarely reported in the literature.…”

Metabolic and Endocrine Challenges

“…Cancer patients on ICI therapy (e.g., ipilimumab and nivolumab) are a novel patient group in whom AC should always be considered, as it may cause severe hypophysitis or adrenalitis. 142 Moreover, several medications interact with steroid metabolism, and can cause AC, including antiepileptic drugs, barbiturates, etomidate, antituberculosis, and antifungal drugs (fluconazole, ketoconazole, voriconazole). Patients with undiagnosed hypoadrenalism can also precipitate an AC in the context of thyrotoxicosis or after the start of thyroxine therapy.…”