Analysis of the Nervous System Adverse Events Associated with Blinatumomab: A Real-World Study Using the FDA Adverse Event Reporting System Database

Background: Nervous system toxicity (NST) is one of the most frequent and dangerous side effects of blinatumomab, which is the world's first bispecific antibody drug targeting both CD19 and CD3. Current clinical trial data do not fully reflect the real-world situation. Therefore, this study evaluated the NST of blinatumomab therapy using the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods: Data were retrieved from FAERS for the period from October 1, 2014 to September 30, 2023. The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence interval progressive neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms were used for data mining. The time to onset (TTO) and clinical outcomes due to blinatumomab-associated NST were assessed.

Results: In the FAERS database, 5,962 adverse reaction case reports primarily implicating blinatumomab were extracted. Male individuals accounted for the highest proportion (2,396 cases, 40.19%) of patients, patients aged 18–45 years old were the most prevalent (1,205 cases, 20.21%), and the majority of reports originated from the United States (3,494 cases, 58.60%), with the highest number of cases reported in 2021 (844 cases, 14.16%). Employing the ROR, PRR, BCPNN, and MGPS methods collectively identified 43 signals of nervous system adverse reactions. Among these adverse reactions, neurotoxicity, neurological symptoms, agnosia, intention tremor, and immune effector cell-associated neurotoxicity syndrome had the highest ROR values. For the neurological events, the median TTO was 3 days, with a range from 1 to 17 days. The highest fatality rate for neurological events was observed in increased intracranial pressure disorders, which also had the highest co-occurrence rate with cytokine release syndrome (CRS) at 36%.

Conclusions: Most NST (79%) did not overlap with cytokine release syndrome.The presence of CRS led to a higher fatality rate in patients experiencing neurological toxicities. In clinical practice, thorough medication evaluation should be conducted prior to administering blinatumomab, especially for high-risk patients with pre-existing neurological conditions.

Keywords: Blinatumomab, Nervous system toxicity, Pharmacovigilance, FDA Adverse Event Reporting System (FAERS)