Abstract
Blinatumomab was active across age and risk groups in patients with relapsed or refractory BCP–ALL.
Major finding: Blinatumomab was active across age and risk groups in patients with relapsed or refractory BCP–ALL.
Clinical relevance: At the determined recommended dose, blinatumomab achieved complete responses in 39% of patients.
Impact: Single-agent blinatumomab therapy warrants further investigation in pediatric patients with BCP–ALL.
The bispecific T-cell engager antibody blinatumomab targets CD19 on B-cell lymphoblasts and has demonstrated clinical activity in adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP–ALL). However, blinatumomab has not been tested in pediatric patients. Von Stackelberg and colleagues investigated the safety and efficacy of blinatumomab in a multicenter, open-label phase I/phase II trial in pediatric patients with relapsed or refractory BCP–ALL. In the dose-escalation phase I study, 49 patients were treated to determine the maximum-tolerated and recommended blinatumomab doses, and 44 patients enrolled in the phase II study received the recommended dose of blinatumomab to determine the complete response rate. Secondary endpoints included the incidence of adverse events, and overall and relapse-free survival. Of the 70 patients in total who received the determined recommended blinatumomab dose, 27 (39%) achieved a complete response within two cycles, including 14 patients who achieved a complete minimal residual disease response. Complete responses were observed in all age groups and across subgroups, including Philadelphia chromosome–positive and MLL-translocated tumors. Adverse events were consistent with what had previously been observed with blinatumomab in adults. The primary treatment-related adverse event leading to permanent treatment discontinuation in two patients was grade 3/4 cytokine-release syndrome, which occurred in 4 patients. The median overall survival for all 70 patients who received the recommended dose was 7.5 months, and the median relapse-free survival among patients who achieved a complete response was 4.4 months. In addition to determining the recommended dose of blinatumomab for pediatric patients with BCP–ALL, this study indicates that blinatumomab has antileukemic activity in pediatric patients with relapsed or refractory BCP–ALL across age groups and in patients with unfavorable cytogenetics and supports its further clinical investigation.
Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.
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