FDA Expands Approval of Blinatumomab for MRD-Positive ALL

The U.S. Food and Drug Administration’s (FDA’s) Oncologic Drugs Advisory Committee voted 8-4 in favor of accelerated approval for the bispecific antibody blinatumomab for the treatment of adults and children with B-cell precursor acute lymphocytic leukemia (ALL) whose disease is in remission but is positive for minimal residual disease (MRD).

“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,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

The decision was supported by data from the single-arm, open-label Study MT 103-203 trial, which assessed blinatumomab in 86 patients with B-cell precursor ALL who were in complete remission (CR) or CR with partial platelet recovery and had detectable MRD (present in ≥1 out of 1,000 cells in their bone marrows). In the trial, 70 patients achieved undetectable MRD, and more than half of the patients remained alive and in remission for at least 22.3 months.

Common AEs associated with blinatumomab included infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, neutropenia, anemia, febrile neutropenia, and thrombocytopenia.

Blinatumomab has a boxed warning that some clinical-trial participants experienced cytokine release syndrome, encephalopathy, or other AEs of the nervous system. Pediatric patients are at risk for serious AEs related to the benzyl alcohol preservative, so the FDA label advises that blinatumomab should be prepared with preservative-free saline for patients weighing less than 48.5 pounds.

The drug previously received priority review and orphan-drug designation for B-cell precursor ALL. The FDA approved blinatumomab under accelerated approval in December 2014 for the treatment of Philadelphia chromosome (Ph)-negative relapsed or refractory positive B-cell precursor ALL. The indication was expanded in 2017 to include patients with Ph-positive ALL.

Source: U.S. Food and Drug Administration press release, March 29, 2018.