Efficacy of levetiracetam prophylaxis in blinatumomab-induced neuro-toxicities in acute lymphoblastic leukemia: Retrospective single-arm cohort study

Abstract

Abstract Background: Blinatumomab, a CD19x3 bispecific T cell engager, shows efficacy for B-cell acute lymphoblastic leukemia. Blinatumomab is associated with different neurotoxicities like seizures, encephalopathy, headaches, and insomnia (Jain et al., 2020). Levetiracetam, an antiepileptic agent, is used as seizure prophylaxis. Its minimal drug interactions promote a potential role in mitigating the adverse events caused by blinatumomab (Zhang et al., 2025). Medical literature reveals the incidence of neurotoxicities but lacks evidence on preventive strategies. Objectives: The primary objective of this study was to assess whether the use of levetiracetam mitigated the severity of Blinatumomab associated neurotoxicities in Acute Lymphoblastic Leukemia. The incidence of neurotoxicities among patients receiving Levetiracetam during Blinatumomab therapy, was compared with historical literature which reported blinatumomab-induced neurotoxicity. The secondary outcome included changes in neurological symptoms and impact of comorbidities on prophylaxis responsiveness. Methods: We used non-probability purposive sampling of ALL patients treated with Blinatumomab from January 2017 to April 2025. This cohort included 14 males and 6 females (n=20). A total of 31 cycles of Blinatumomab were administered. The exposure group consisted of patients receiving Levetiracetam prophylaxis (most patients received 500mg PO twice daily for 35 days /cycle) along with their Blinatumomab therapy for B-ALL, while comparative data of neurotoxicity rates from published literature in which Blinatumomab was used without any prophylactic antiepileptics served as a control. Data were collected via EMRs and supplemented with physical file review. Those that did not receive prophylaxis or had a history of brain lesions were excluded. Blinatumomab neurotoxicity grading scale, adapted from CTCAE v4.03 was utilised in categorizing levels of neurologic adverse events (NAEs). Results: 19 patients (1 excluded for a brain lesion) with B cell Acute Lymphoblastic Leukemia (B-ALL), received 31 cycles of Blinatumomab between January 2017 and April 2025, were included in the study. The median age was 21 years (Range: 4-62). Presence of CNS leukemia was checked via CSF cytology. Post Blinatumomab 2 patients developed CNS leukemia Relapse / atypical cells which later cleared. Neurotoxic side effects occurred in 9 out of 31 cycles (29.03%). Among these, seizures occurred in 1 cycle (3.23%), headache in 5 cycles (16.13%), aphasia in 1 cycle (3.23%) and insomnia in 1 cycle (3.23%). Comparative analysis with previously published data revealed incidence of neurotoxicity as 29.03% vs 65%, which was significantly lower (p<0.0001; 95% CI [0%, 45.19%]), headache as 16.13% vs 39%, significantly lower (p=0.0055; 95% CI [0%–30.96%]), insomnia as 3.23% vs 31%, significantly lower (p=0.0002; 95% CI [0%, 14.41%]). No significant difference in seizures (3.23% vs 2-8%, upto 17% in Down's Syndrome, p=0.87(2%), p=0.2787(8%); 95% CI [0%, 14.41%]) and aphasia (3.23% vs 12%; p=0.0994; 95% CI [0%, 14.41%]) likely due to small sample size. The study had 2 limitations. Firstly, it has a small sample size with 19 patients and 31 cycles which limit the universality of findings. Secondly, the absence of a control group due to single arm design of study. Comparative analysis was done with published data. Conclusion: This retrospective single-arm cohort analysis indicates that prophylactic Levetiracetam administration can significantly lower the occurrence of Blinatumomab related neurological toxicities in patients with B-cell Acute Lymphoblastic Leukemia. Reduction, especially in headache, insomnia, and total neurological adverse events, identifies Levetiracetam as a promising neuroprotective drug in Blinatumomab treatment. These conclusions warrant further confirmation by prospective RCTs to define its efficacy as a regular preventive measure.