March 29, 2018—Today, the U.S. Food and Drug Administration (FDA) granted accelerated approval to blinatumomab for the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia (ALL) who are in remission but still have minimal residual disease (MRD). Blinatumomab is a bi-specific T-cell engager (BiTE) monoclonal antibody directed towards B-cell surface protein CD19.

“This is the first FDA-approved treatment for patients with MRD-positive ALL,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence in a statement. “Because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer.”

This accelerated approval follows results from the phase II BLAST trial (NCT01207388) investigating the antibody in patients with B-cell precursor ALL in complete remission (CR) or CR with partial platelet recovery and detectable MRD >0.1% (at least 1 out of 1,000 bone marrow cells) reported in Blood earlier this year. The primary endpoint of BLAST was complete MRD response, defined as MRD <0.01% (at most 1 out of 10,000 cells) after 1 cycle of blinatumomab.

In the trial, 88 of 113 evaluable patients (78%) achieved a complete MRD response. Analysis showed, participants who achieved a complete MRD response maintained longer relapse-free survival than patients who remained MRD-positive (23.6 months compared with 5.7 months). Further, overall survival was 38.9 months compared with 12.5 months, for patients who achieved a complete MRD response and who remained MRD-positive, respectively.

As blinatumomab was approved under the accelerated approval pathway, further study in randomized controlled trials is required to verify benefit to overall survival or disease-free survival in patients with ALL. “Studies are being conducted to assess how [blinatumomab] affects long-term survival outcomes in patients with MRD,” said Pazdur.

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Jonathan A. Bell
Published Online: Thursday, March 29, 2018