Recognizing Delayed ICANS: A Case of CAR T-Cell Therapy-Associated Neurotoxicity

Case Diagnosis: Immune effector cell-associated neurotoxicity syndrome

Case Description or Program Description: A 54 year old male with stage 4 high-grade diffuse B-cell lymphoma with CNS involvement receiving intrathecal methotrexate and underwent CAR T-cell therapy 5 weeks prior, presented with shortness of breath, progressive lower extremity weakness leading to a fall. Initial workup revealed multifocal pneumonia and pancytopenia treated with antibiotics and multiple transfusions, respectively.
MRI brain revealed increased bilateral cerebral disease and new bilateral cerebellar white matter disease, likely secondary to chemotherapy. CSF analysis showed no malignancy. Throughout his hospital course, the patient developed disorientation, word-finding difficulty and further ascending weakness involving his arms. Lumbar puncture was deferred due to hyperreflexia. The patient was diagnosed with grade 1 ICANS and methotrexate induced leukoencephalopathy and was treated with a 7 day course of IV dexamethasone, followed by a taper.

Setting: Tertiary care hospital

Assessment/Results: The patient was started on a 7 day course of IV steroids followed by a taper, which improved his symptoms. Toclizumab, IL-6 therapy, was not needed as the patient did not have concurrent cytokine release syndrome (CRS). He was recommended for acute rehabilitation following discharge.

Discussion (relevance): The patient’s rapid progression of weakness was crucial to rule out AIDP. His hyperreflexia made GBS less likely and there was no evidence of malignancy on imaging or CNS analysis. This case is atypical because most ICANS cases present 3-5 days following CAR T-cell therapy, though a minority of patients experience a “delayed ICANS’ > 3 weeks post-infusion. ICANS is a clinical diagnosis and symptoms range from mild confusion to ataxia, seizures, and coma.

Conclusions: This case emphasizes the importance of recognizing ICANS in patients undergoing CAR T-cell therapy, regardless of neurotoxic symptom onset.