NCMP-35. ICANS and seizure-like activity observed after treatment with glofitamab in patient with diffuse large B-cell lymphoma: a case report

T-cell engagers represent a promising immunotherapy class that is increasingly being used to treat hematologic malignancies. Glofitamab is a bispecific monoclonal antibody that binds both CD20 receptors on B cells and CD3 receptors on T cells, leading to T-cell activation and lysis of malignant B cells. Glofitamab was approved in the United States in 2023 to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma who have failed at least two lines of treatment. At that time, incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) in patients treated with glofitamab was estimated to be relatively rare, at 4.8%. ICANS can occur with use of certain immunotherapies and can present with various neurologic symptoms, such as headaches, tremors, encephalopathy, hallucinations, and seizures. The patient is a 78-year-old female with aggressive DLBCL which was poorly responsive to several lines of therapy, including 4 cycles of mini R-CHOP, 4 cycles of Pola-BR, and gemcitabine oxaliplatin. Glofitamab, with obinutuzumab pretreatment, was started as a disease-holding bridging therapy while insurance approval for CAR T-cell therapy was in process. Four days after second dose of glofitamab, patient started to experience episodes of horizontal nystagmus and altered awareness concerning for non-convulsive seizures. ICANS was suspected given absence of clear infectious source, metabolic disorder or CNS metastasis. Patient was treated with IV steroids (initially IV dexamethasone 10 mg q6 hours followed by IV methylprednisolone 1g daily then IV dexamethasone taper), levetiracetam (1000 mg q12 hours IV) and, briefly, with anakinra (100 mg q6 hours) with resolution of nystagmus, seizure-like activity and altered mental status. This case is an example of ICANS presenting with seizure-like activity and altered mental status in a patient treated with glofitamab. Additional studies are needed to understand the pathophysiology and management of glofitamab-induced ICANS.