Reactions Weekly | 2021
Brexucabtagene autoleucel
Abstract
Cerebral oedema and cytokine release syndrome: case report A 65-year-old man developed cytokine release syndrome (CRS) and cerebral oedema during treatment with brexucabtagene autoleucel for mantle cell lymphoma. The man was diagnosed with stage IV relapsed/refractory pleomorphic mantle cell lymphoma. Subsequently, he received leukapheresis with optional bridging therapy, followed by conditioning chemotherapy (cyclophosphamide and fludarabine. Following leukapheresis, he started receiving conditioning chemotherapy, followed by brexucabtagene autoleucel [KTE-X19] infusion at a target dose of 2χ106 CAR T cells/kg on day 0. Before infusion, prophylactic treatment with levetiracetam was initiated. After 24h of brexucabtagene autoleucel infusion, he developed grade I CRS. Hence, the man was treated with tocilizumab. He also received aztreonam and vancomycin for non-neutropenic fever. He had delayed speech and thought processes with handwriting changes, memory deficit and slight tremor. His symptoms were consistent with grade II encephalopathy. On day 3, he presented with marginal leucopenia. His chest X-ray revealed multifocal opacities. He received off-label treatment with IV siltuximab 11 mg/kg for grade II CRS. On day 4, treatment with methylprednisolone was initiated. After some improvement, his condition deteriorated. Hence, the second dose of tocilizumab was given. Afterwards, he was transferred to the ICU for worsening aphasia, obtundation and confusion. He was intubated for airway protection. He had 2 tonic-clonic seizures. The MRI revealed diffuse gyral swelling, and an EEG revealed triphasic waves with diffuse disturbances. The MRI findings confirmed cerebral oedema. Subsequently, a diagnosis of grade IV encephalopathy was made. Treatment with mannitol was initiated, along with steroids. In spite of treatment, no improvement was observed on day 5. He developed grade III transaminase elevation. His CSF was clear with increased opening pressure to 20cm H2O. His CSF protein and glucose level were increased. Cytology revealed increased WBC and atypical and activated lymphocytes (mainly T cells) admixed with histiocytes and neutrophils (78%). Due to worsening neurological symptoms, he was treated with hydrocortisone and cytarabine [ara-C]. On day 6, EEG revealed bihemispheric cortical dysfunction, and the MRI revealed cerebral oedema and sulcal hyperintensity. He had neurosurgery was performed for placement of an external ventricular drain. He received prophylactic acyclovir for the risk of infection. After no improvement, antithymocyte globulin [ATG] was given with increased methylprednisolone and the third dose of tocilizumab. On day 7, an MRI revealed stable changes. Therefore, two doses of antithymocyte globulin were given, which resulted in the resolution of transaminase elevation. On day 11, he was extubated. Over the following 11 days, he received tapering doses of methylprednisolone with remarkable clinical improvement. On day 14, the ventricular drain was removed, and the encephalopathy was resolved. On day 20, an MRI showed considerably improved periventricular white matter T2 hyperintensity and resolution of abnormal signal in the dorsal brainstem/ thalami. Therefore, he was discharged to the rehabilitation facility with tapering doses of oral corticosteroids. Two months after initiation of brexucabtagene autoleucel, brain MRI findings completely resolved. At a 24-month follow-up, he was in complete remission without any neurologic or cognitive deficits.