Effect of Methylphenidate and Duloxetine on Neurotoxicity in CAR-T: A Case Study

Abstract

Introduction Chimeric Antigen Receptor (CAR) T-cell therapy is a promising therapy for B-cell malignancies; however, it is associated with serious adverse effects including cytokine release syndrome and neurotoxicity. The incidence of neurotoxicity in two landmark trials ranged from 40-64%.1,2 Common signs and symptoms of neurotoxicity may include confusion, delirium, tremor, agitation, headache, personality changes, somnolence and dysphasia/aphasia. We report a case of severe neurotoxicity followed by significant depression and abulia. Methods We reviewed the case of a patient who experienced neurotoxicity after CD19 directed CAR T-cell therapy. The patient developed grade 2 neurotoxicity by CTCAE v4.0 consisting of aphasia, facial droop, nystagmus, tongue fasciculations, handwriting changes, and paranoid delirium. The patient was treated with intravenous dexamethasone 10mg every 6 hours with worsening of neurotoxicity during steroid taper. The patient was discharged on oral dexamethasone when medically stable then subsequently readmitted with different neurocognitive manifestations including failure to thrive, profound personality changes, passive suicidal ideation, abulia, paranoia, depression, and weakness. The patient had stopped taking all medications, including steroids, and refused all medical care. Steroids were not restarted due to steroid myopathy and psychosis. Infectious and structural complications were ruled out. Physical Medicine and Rehabilitation (PMR) was consulted. Based on evidence-based neuro-rehabilitation interventions, methylphenidate and duloxetine were recommended. Results The patient was started on methylphenidate 10mg twice daily and duloxetine extended release 30mg daily. Within 24 hours, the patient showed marked improvement with motivation to participate in medical care, improvement in anhedonia, and resolution of passive suicidal ideation. The patient showed significant improvement in physical function after participation in a multimodal inpatient rehabilitation program. Conclusion Significant improvement in neurocognitive function was seen within 24 hours after the initiation of methylphenidate and duloxetine. We propose this drug combination as a potential treatment in CAR-T patients with neurocognitive dysfunction as sequelae of neurotoxicity.