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.

Severe cytokine release syndrome induced by immune checkpoint inhibitors in cancer patients – A case report and review of the literature

“…Subsequently, an additional seven papers were excluded upon closer inspection, as they pertained to hemophagocytic lymphohistiocytosis, capillary-leak syndrome, or anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. In total, we accurately summarized 22 papers [ [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. A total of 49 patients were enrolled.…”

Cellular and Molecular Mechanisms of Pathogenic and Protective Immune Responses to SARS-CoV-2 and Implications of COVID-19 Vaccines

“…Initially, it was assumed that virus-induced cytopathic effects are mainly responsible for the clinical features of COVID-19. However, with the advent of severe COVID-19 and analysis of patients with pneumonia and MOF, there are various pieces of scientific evidence indicating that the virus can escape from the upper to lower respiratory tract, which may be responsible for the lethal inflammatory response observed in some patients, known as cytokine release syndrome (CRS) [ 91 , 92 , 93 , 94 ].…”

SARS-CoV-2 infection and COVID-19 vaccination in cancer patients undergoing immune checkpoint inhibitors

“…The plausible explanation for this view is related to the mechanism of further damage of respiratory epithelium caused by overactivation of T cells [ 17 ]. Murata et al reported a 70-year-old man who had been treated with nivolumab and ipilimumab for lung cancer and was diagnosed with CRS due to systemic symptoms with inflammation and elevated IL-6 after SARS-CoV-2 infection [ 51 ]. The authors deem that the patient showed a good response to immunotherapy, and the occurrence time of CRS coincided with the time of SARS-CoV-2 infection.…”

“…The authors deem that the patient showed a good response to immunotherapy, and the occurrence time of CRS coincided with the time of SARS-CoV-2 infection. It is considered that CRS may be irAEs caused by infection [ 51 ].…”

“…CRS is a systemic inflammatory disease that begins with fever and is featured by high cytokine release, especially for IL-6, triggered by infection or medication [ 72 ]. Murata et al summarized previously reported CRS cases induced by ICIs, and IL-6 levels varied greatly among different cases [ 51 ]. The research found that IFN-γ enhances IL-6 production in monocytes [ 73 ] and involved in the development of ARDS in COVID-19 [ 22 ], while IFN signaling is the pathway leading to PD-1/PD-L1 expression [ 74 ].…”