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.
