(025) Characterization of CTCAE grading of blinatumomab-associated neurotoxicity and the corresponding treatment disruptions

Poster Abstract:

Background: Blinatumomab is a bispecific CD19-directed CD3 T-cell engager (BiTE) approved for the treatment of CD19 positive B-cell acute lymphoblastic leukemia (ALL). It has a black box warning of neurological toxicities, which may be severe, life-threatening, or fatal. Neurotoxicity is graded using the Common Criteria for Adverse Events (CTCAE). In clinical trials, blinatumomab-associated neurotoxicity (BNT) was most often reported during the first cycle, with 65% of all patients experiencing BNT of any grade (most commonly low-grade headache and tremor). Grade 3 BNT occurred in 13% of patients (encephalopathy, confusion, somnolence, seizure) with dose interruptions occurring in about 10% of patients and treatment discontinuation occurring in approximately 3% of patients. The FDA labeling has recommendations for dose interruptions or discontinuations if a patient experiences BNT based on the corresponding CTCAE grade. The CTCAE scale is very subjective in nature using generalized terminology such as “mild” and “moderate” and considers limitations on activities of daily living (which are hard to assess in acute situations in the inpatient setting) for severity of symptoms. This may lead to inaccurate grading of BNT which may cause unnecessary interruptions in patients’ treatments, longer hospitalization times, and decreased effectiveness of therapy.

Objective: At VCU Health System (VCUHS), there are inconsistencies in grading of BNT events, which has led to confusion on how to advise proper dose interruptions, reductions, or discontinuations. The goal is to implement protocolized recommendations at VCUHS surrounding the safety of administration of blinatumomab.

Methods: This is a retrospective chart review from December 2014 – September 2023 of adult patients diagnosed with B-cell ALL who have received blinatumomab at VCUHS. The primary objective is to characterize the grading and incidence of BNT and subsequent treatment disruptions that have occurred at VCUHS. A secondary objective is to characterize the impact of BNT on achievement of complete remission (CR) and minimal residual disease (MRD) negativity. Blinatumomab associated neurotoxicity events along with the corresponding CTCAE grade, the extent of treatment interruptions, achievement of complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), and achievement of MRD negativity will be recorded.

Results/

Conclusion: Results identified in this project will assist in development and implementation of a VCUHS protocol regarding assessment and grading of BNT and recommendations for subsequent dose modifications.

References (must also be included in final poster): 1. Blincyto (blinatumomab) [package insert]. Thousand Oaks, California: Amgen; 2023.
2. Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017;376(9):836-847. doi:10.1056/NEJMoa1609783
3. Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131(14):1522-1531. Blood. 2019;133(24):2625. doi:10.1182/blood.2019001109