AI Article Synopsis
- Blinatumomab is a specialized antibody treatment targeting CD19 in children with relapsed or refractory B-cell acute lymphoblastic leukemia (BCP-ALL) and was tested in a study focusing on safety, dosage, and effectiveness.
- The study included 49 children in phase I and 44 in phase II, determining a maximum-tolerated dosage of 15 µg/m/d, with a recommended starting dose of 5 µg/m/d.
- Results showed that 39% of patients achieved complete remission within the first two treatment cycles, indicating that blinatumomab could be a promising therapy for pediatric patients with this type of leukemia.
Article Abstract
Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m/d for the first 7 days, followed by 15 µg/m/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.
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| http://dx.doi.org/10.1200/JCO.2016.67.3301 | DOI Listing |
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