Severe Cytokine Release Syndrome and Immune Effector Cell-associated Neurotoxicity Syndrome in a Man Receiving Immune Checkpoint Inhibitors for Lung Cancer

Abstract

A 55-year-old man with stage IV lung adenocarcinoma was treated with cisplatin, pemetrexed, nivolumab, and ipilimumab. Approximately 100 days after treatment initiation, he became disoriented and presented to the emergency department with a high fever. Blood tests revealed liver and kidney dysfunctions. Subsequently, the patient developed generalized convulsions that required intensive care. He was clinically diagnosed with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Organ damage was gradually controlled with immunosuppressive drugs, including steroids, and the patient was discharged. Successful treatment is rare in patients with CRS, including ICANS, during immune checkpoint inhibitor treatment for solid tumors.

Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report

“…There was no acute fever, electrolyte disturbance, carcinomatosis, brain metastasis, head trauma, illicit drug dependence, or insomnia that could explain the occurrence of seizures. Second, ICANS has already been reported in association with CD20 blockers [ 2 , 11 ]. Tanaka et al reported the case of a 55-year-old male with lung cancer who was treated with cisplatin, pemetrexed, nivolumab, and ipilimumab and developed ICANS 100 days after starting therapy [ 2 ].…”

“…Second, ICANS has already been reported in association with CD20 blockers [ 2 , 11 ]. Tanaka et al reported the case of a 55-year-old male with lung cancer who was treated with cisplatin, pemetrexed, nivolumab, and ipilimumab and developed ICANS 100 days after starting therapy [ 2 ]. The patient suffered from high fever, disorientation, and seizures and responded positively to glucocorticoids and immunosuppression [ 2 ].…”

“…Immune effector cell-associated neurotoxicity syndrome (ICANS) is a newly described side effect that typically occurs after the use of chimeric antigen receptor (CAR) T-cell therapy in 20%-60% of cases [ 1 ], but is rarely also caused by immune checkpoint inhibitors (e.g., monoclonal antibodies (CD20 blockers)) [ 2 ]. The severity of ICANS varies significantly between mild manifestations and persistent, fatal cerebral edema [ 1 ].…”

“…Immune effector cell-associated neurotoxicity syndrome has also been reported during monoclonal antibody therapy [ 2 ]. One of these is glofitamab, a bispecific monoclonal antibody (CD20-directed CD-3 T-cell engager) for the treatment of large B-cell lymphoma [ 3 ].…”

Fever of unknown origin associated with immune checkpoint inhibitors

“…Cytokine release syndrome (CRS) is relatively rare in patients treated with ICIs, as evidenced by an incidence of approximately 4.6% reported in a single-center retrospective study ( 19 , 97 , 98 ). However, once it occurs, it tends to be persistently severe and potentially life-threatening ( 99 , 100 ). CRS, as a systemic inflammatory response mediated by inflammatory cytokines, is directly triggered by immunotherapy.…”