A case of cytokine release syndrome accompanied with COVID-19 infection during treatment with immune checkpoint inhibitors for non-small cell lung cancer

Abstract

Cytokine release syndrome (CRS) is a systemic inflammatory disease caused by a variety of factors, including infections and certain drugs. A 70-year-old man who was diagnosed with a postoperative recurrence of lung adenocarcinoma received nivolumab, ipilimumab, pemetrexed and carboplatin every 3 weeks for two cycles followed by nivolumab and ipilimumab, which resulted in a partial response. Four days after the dose of nivolumab, the patient returned with diarrhea and fever. The patient was diagnosed with COVID-19 infection accompanied by severe colitis. Although intensive care was performed, the patient suddenly went into cardiopulmonary arrest. Examination revealed an abnormally high interleukin-6 level, suggesting CRS. This is the first report of a patient with CRS accompanied with COVID-19 infection during treatment with ICIs. Cytokine release syndrome (CRS) is a systemic inflammatory disease caused by a variety of factors, including infections and certain drugs. Here, we report a case of non-small cell lung cancer with CRS caused by COVID-19 infection during treatment with nivolumab and ipilimumab. Fever is a common event in cancer patients, especially in COVID-19-infected patients, but when fever develops during cancer immunotherapy, CRS should always be kept in mind.

Keywords: SARS-CoV-2; cancer immunotherapy; cytokine release syndrome; immune-related adverse events.

FIGURE 1

Clinical course of lung adenocarcinoma. Lung adenocarcinoma recurred 5 months prior to admission, and nivolumab plus ipilimumab was started combined with two cycles of carboplatin and pemetrexed. After two and four cycles of therapy, contrast‐enhanced computed tomography (CT) showed that the tumor had decreased in size. Three months prior to admission, the patient developed grade 2 hypophysitis (isolated adrenocorticotropic hormone deficiency) as an immune‐related adverse event. Immunotherapy was stopped, then restarted a month and a half later. CT showed no tumor regrowth just 4 days prior to admission. The final dose of nivolumab was administered on this day. Four days after resuming treatment with nivolumab, the patient returned with diarrhea and high fever. The patient was diagnosed with COVID‐19 infection and suggested cytokine release syndrome. Findings of thin‐section computed tomography. (a) Transition of CT findings over time. The lung adenocarcinoma shrank after the start of treatment and did not regrow. (b) Chest CT on admission. There was no evidence of pneumonia or acute respiratory distress syndrome which would indicate COVID‐19 infection in the lung fields. (c) Abdominal CT on admission. Bowel edema suspicious of colitis was present