Abstracts

Rationale: Background: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. Autologous chimeric antigen receptor T-cells (CARTs) therapy is used for treatment of refractory and relapsed hematological malignancies, DLBCL being one of them. Although several studies have shown success with CART in patients with DLBCL, neurotoxicity associated with CAR T cell therapy remains idiosyncratic and poorly characterized. In literature patients are described as variably suffering from encephalopathy, delirium, aphasia, tremor, ataxia seizures and cerebral edema.Aim: The primary aim of this study was to evaluate the neurological and EEG outcome of patients who received CART therapy for thirty days along with seizure prophylaxis with levetiracetam per institutional policy. The secondary aim was to assess safety and tolerability of levetiracetam in this cohort. Methods: We performed a retrospective review of all the patients that underwent CART therapy at our institution between August 2018 to February 2019. Per institutional protocol, every patient was evaluated by neurology team on day of admission and started on levetiracetam 750mg twice daily from Day 1 to Day 30 of treatment. They also had daily CAR-T-cell-therapy-associated TOXicity (CARTOX) 10 scoring. We reviewed patient characteristics including gender, age, history of seizures, use of anti-seizure medication, seizures during therapy, seizures during follow up, development of Cytokine release syndrome (CRS ) and/or CRES (CART related encephalopathy syndrome), adverse effects from anti-seizure medications and EEG findings. Results: We identified a cohort of eight patients. Five patients were male and three were female. Median age was fifty-nine years. None of the patients had a history of seizures. All except one patient developed CRS and/or neurotoxicity. Four patients developed CRES grade 2/3 and received intravenous dexamethasone, one patient had grade 1 CRES and did not require any IV steroids. Three patients developed CRS and required IV Tocilizumab. Two patients developed both CRS as well as CRES. However, none of the patients developed seizures during CART therapy for thirty days. Levetiracetam was discontinued in five patients at the time of discharge and in two patients as they transitioned to hospice soon after. One patient was continued on levetiracetam due to unclear reasons which was discontinued eventually before follow-up. One of the two patients transitioned to hospice was due to cancer progression and the second patient had respiratory failure with terminal extubation. During follow up, none of the remaining six patients reported seizures. None of the patients reported any adverse effects due to levetiracetam prophylaxis during treatment and follow up. Routine EEG showed diffuse slowing with no epileptiform activity in five patients. No EEG was obtained in three patients. Conclusions: Anti-seizure medications like levetiracetam have been used for seizure prophylaxis after traumatic brain injury, sub arachnoid hemorrhage, etc. CART therapy is associated with seizures as one of the manifestations of neurotoxicity. However, currently we do not have any guidelines regarding use of anti-seizure medications for seizure prophylaxis in patients receiving CART therapy. Levetiracetam was found to be safe and well tolerated in our study. Limitations of our study include small sample size and retrospective data. Further studies will be valuable to elucidate the efficacy and cost-benefit analysis of routine seizure prophylaxis in this patient population. Funding: No funding