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.

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2025
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