Neurologic adverse events in patients with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab: management and mitigating factors.

Abstract

Neurologic events (NEs) have been reported during treatment with blinatumomab, a bispecific T cell engager (BiTE®) construct. We evaluated the occurrence, severity, and management of NEs; the relationship between NEs and blinatumomab dose; and the potential clinical risk factors in an open-label, single-arm, phase 2 study (N = 189). Patients had Philadelphia chromosome-negative, relapsed/refractory acute lymphoblastic leukemia (ALL) and ≥ 10% bone marrow blasts. The relationship between blinatumomab exposure and NE incidence and severity was assessed. Clinical risk factors for NEs were assessed in a post hoc multivariate analysis. Overall, 98 patients (52%) experienced NEs: most frequently, dizziness, tremor, confusional state, and encephalopathy. NEs occurred predominantly during cycle 1 (median onset, 9 days) and were usually grades 1 or 2. Grade ≥ 3 NEs (13-17% incidence), serious NEs (16-19% incidence), and recurring NEs were managed with infusion interruptions or dexamethasone treatment. The incidence of NEs increased with increasing blinatumomab exposure at a given dose, but exposure appeared unrelated to NE severity. NEs were more frequent in patients ≥ 65 years than < 65 years (72 vs 49%). In a multivariate analysis, race other than white (hazard ratio [HR], 2.11; P = 0.009), > 2 prior salvage therapies (HR, 2.48; P = 0.006), and prior NEs (HR, 1.65; P = 0.020) were risk factors for time to first on-study NE. Although the mechanism underlying NEs associated with blinatumomab treatment in patients with relapsed/refractory ALL remains unclear, NEs tended to occur early during treatment and were often resolved by interrupting treatment and with dexamethasone. Additional research is warranted to investigate the risk factors for NEs.

• Authors: Anthony S Stein, Gary Schiller, Ramsis Benjamin, Catherine Jia, Alicia Zhang, Min Zhu, Zachary Zimmerman, Max S Topp
• Journal: Annals of hematology (Ann Hematol) Vol. 98 Issue 1 Pg. 159-167 (Jan 2019) ISSN: 1432-0584 [Electronic] Germany
• PMID: 30238148 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antibodies, Bispecific
• blinatumomab
• Dexamethasone

Topics

• Adolescent
• Adult
• Age Factors
• Aged
• Antibodies, Bispecific (administration & dosage, adverse effects)
• Blast Crisis (drug therapy, epidemiology)
• Dexamethasone (administration & dosage)
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Nervous System Diseases (chemically induced, drug therapy, epidemiology)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, epidemiology)
• Recurrence
• Risk Factors
• Severity of Illness Index