Blinatumomab: A novel, bispecific, T-cell engaging antibody

Purpose. The pharmacology, pharmacodynamics, pharmacokinetics, efficacy in clinical trials, safety and tolerability, and place in therapy of blinatumomab are reviewed. Summary. Blinatumomab is a novel, bispecific, T-cell engaging antibody that targets tumor-associated antigens CD19 and CD3. Blinatumomab was approved through an accelerated pathway for the treatment of Philadelphia (Ph) chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). One Phase II trial found 16 of 21 patients to be negative for minimal residual disease (MRD) after one cycle of treatment, resulting in a response rate of 80%. Another Phase II trial showed an 82% MRD response, even in heavily pretreated patients. The most common adverse events of any grade noted were pyrexia, febrile neutropenia, hypokalemia, and anemia. The most fre-quently occurring grade 3 or 4 adverse events were febrile neutropenia, neutropenia, and anemia. Cycle 1 is dosed as a mu g/day continuous i.v. infusion on days 1-7 and a 28-mu g/day continuous i.v. infusion on days 8-28 administered as a four-week continuous i.v. infusion, followed by at least two weeks of no treatment. Subsequent cycles are dosed as a 28-mu g/day continuous i.v. infusion on days 1-28, followed by at least two weeks of no treatment, for up to five treatment cycles. Conclusion. Blinatumomab is approved as an option for Ph chromosome-negative relapsed or refractory B-cell precursor ALL and is a needed addition to the limited treatment options for this difficult-to-treat patient population. Two Phase II clinical trials resulted in impressive results when using blinatumomab as a single agent, resulting in the drug's approval.