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FDA Grants sBLA for Blinatumomab in Pediatric Patients With Ph–Negative Relapsed/Refractory B-Cell Precursor ALL

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Amgen announced on May 3 that the U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental Biologics License Application (sBLA) for blinatumomab (Blincyto) to include new data supporting the treatment of pediatric and adolescent patients with Philadelphia chromosome–negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Blinotumomab is in the bispecific T-cell engager (BiTE) class of constructed monoclonal antibodies. It specifically targets the CD19 antigen present on B cells.

“Children and adolescents with ALL who experience a second or greater relapse or are refractory often have a dismal prognosis, with survival rates below 10%,” said Sean E. Harper, MD, Executive Vice President of Research and Development at Amgen. “The FDA's acceptance of the sBLA submission for [blinatumomab] reinforces immunotherapy as a potential option for children in need of new treatments to fight this complex disease and help prevent further relapse.”

Phase I/II Study

The sBLA is based on data from a phase I/II single-arm, multicenter, dose-finding, efficacy trial that evaluated blinatumomab in patients less than 18 years old with B-cell precursor ALL that was refractory, had relapsed at least twice, or relapsed after an allogeneic hematopoietic stem cell transplant.

This study included a phase I dose-finding portion and a phase II portion evaluating safety and efficacy at the recommended dose (stepwise 5–15 μg/m²/d), which was proposed by an independent Data Safety Monitoring Board based on data from the dose-finding portion. The primary phase I endpoint was the maximum-tolerated dose, defined as the maximum dose at which ≤1 of 6 patients experienced a dose-limiting toxicity. Secondary endpoints included pharmacokinetics and incidence of adverse events.

The primary phase II endpoint was complete remission within the first two cycles of blinatumomab treatment. Secondary endpoints included incidence of adverse events, proportion undergoing allogeneic hematopoietic stem cell transplant after blinatumomab treatment, relapse-free survival, and overall survival. Minimal residual disease response and complete minimal residual disease response were exploratory endpoints in both phases.

The most frequent grade ≥ 3 adverse events among the 70 patients who received the recommended dose were anemia, thrombocytopenia, febrile neutropenia, hypokalemia, and neutropenia. The FDA-approved prescribing information for blinatumomab includes a boxed warning for cytokine release syndrome and neurologic toxicities.

Treatment in this study has been completed, and subjects are being monitored for long-term efficacy. The data are being submitted for publication.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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