# Case Report: Safety analysis of blinatumomab consolidation therapy in two cases of acute B-cell lymphoblastic leukemia in complete remission complicated with immune effector cell-associated neurotoxicity syndrome

## TL;DR

This case report examines the safety of blinatumomab in two B-cell leukemia patients who developed neurotoxic side effects, highlighting the need for careful monitoring and individualized treatment.

## Contribution

The paper provides insights into managing immune effector cell-associated neurotoxicity syndrome (ICANS) in patients undergoing blinatumomab therapy.

## Key findings

- ICANS symptoms varied between patients and resolved with interventions like levetiracetam and corticosteroids.
- Elderly patients and those with specific genetic mutations may face higher ICANS risks.
- Close monitoring of neurological and cytokine markers is recommended for high-risk patients.

## Abstract

Blinatumomab, a bispecific T-cell engager (BiTE), has significantly improved the efficacy of B-ALL treatment. However, its association with immune effector cell-associated neurotoxicity syndrome (ICANS) has garnered increasing attention. This study analyzes two cases of ICANS to explore the challenges in recognizing clinical symptoms and standardizing management.

Case 1 involved a 69-year-old male with B-ALL, harboring TP53 and DNMT3A mutations, who developed grade 2 ICANS following blinatumomab treatment. Therapy was continued without interruption, and symptoms resolved with levetiracetam intervention. Case 2 was a 29-year-old male with B-ALL and ETV6::RUNX1 fusion gene, who developed grade 4 ICANS (seizures, impaired consciousness, epileptic episodes) on day 4 of blinatumomab therapy. The patient required intensive care and comprehensive intervention, leading to symptom resolution but discontinuation of treatment. Neither case exhibited central nervous system infiltration, and cranial CT scans showed no abnormalities.

ICANS may be associated with cytokine release, blood-brain barrier disruption, and genetic background, presenting with heterogeneous symptoms. Elderly patients or those with specific genetic mutations may face increased risks, necessitating individualized dose adjustments (e.g., stepwise dosing) and close monitoring of neurological functions and cytokines (e.g., IL-6). Early recognition of subtle symptoms (e.g., tremors) combined with corticosteroids and antiepileptic drugs can improve outcomes. The use of blinatumomab requires careful balancing of efficacy and neurotoxicity, particularly in high-risk patients. This case report provides valuable insights for the clinical recognition and management of ICANS.