Single-agent blinatumomab demonstrated antileukemia activity in pediatric patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in a recently published phase I/II study.
Single-agent blinatumomab demonstrated antileukemia activity in pediatric patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in a phase I/II study published recently in the Journal of Clinical Oncology by Arend von Stackelberg, MD, of CharitÃ© Campus Virchow-Klinikum in Berlin, and colleagues.
Based on data from this study, blinatumomab, a bispecific T-cell engager antibody construct targeting CD19, was approved by the US Food and Drug Administration in September for the treatment of pediatric patients with Philadelphia chromosome-negative relapsed or refractory BCP-ALL. The drug was granted accelerated approval.
Prior to this approval, children with second or greater relapsed or refractory BCP-ALL had poor prognosis when treated with combination chemotherapy and transplant. In an adult study of blinatumomab, patients with relapsed or refractory disease had a response rate of 43% with single-agent treatment.
This phase I/II study enrolled 49 children aged younger than 18 in a phase I dosage-escalation study, and 44 children in a phase II study using 6-week treatment cycles. The primary endpoints were maximum tolerated dose and complete remission rates within the first 2 cycles.
During phase I, four patients had dose-limiting toxicity; three had grade 4 cytokine-release syndrome and one had fatal respiratory failure. The researchers determined the maximum-tolerated dose was 15 mcg/m2 per day.
For the phase II study, patients were given 5 mcg/m2 per day for the first week followed by a dose of 15 mcg/m2 per day. Overall 70 patients received the recommended dose. Among these patients, 39% achieved a complete remission within the first 2 cycles of treatment. More than one-half (52%) achieved complete minimal residual disease response (MRD). Of the 27 patients who responded to treatment with the recommended dose, four were still in remission at the end of the 2-year follow-up.
“Blinatumomab showed antileukemic activity across all age groups, including patients < 2 years old and those with unfavorable cytogenetics,” the researchers wrote. “Given the heavily pretreated population, we consider the complete response rate to be clinically satisfactory, particularly in light of the observed toxicities.”
A subgroup analysis showed a complete remission rate of 56% in patients with less than 50% bone marrow blasts at baseline compared with 33% among those with 50% or more blasts. Additionally, two of three patients with Philadelphia-positive disease and one of four patients with hypodiploidy achieved complete remission.
The most frequent grade 3 or worse adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%).
“This study supports further evaluation of blinatumomab in children with BCP-ALL, including those with first-relapse or newly diagnosed disease at high risk of treatment failure because of significant MRD burden or unfavorable cytogenetics,” the researchers wrote.