Update on Use of Immunotherapy in Hematologic Malignancies - Episode 5
Blinatumomab, an immunotherapy antibody that targets the CD19 antigen expressed on B-cells, was approved by the FDA patients with Philadelphia chromosome-negative, relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL) in December 2014. This accelerated approval was based on a 32% complete remission (CR) rate that lasted a median of 6.7 months. Additionally, 31% of the patients had a CR with or without complete hematological recovery that was minimal residual disease negative.
Blinatumomab engages T-cells to activate and cause cell lysis of leukemic cells. The agent is a bispecific CD19 and CD3 T-cell engager that activates endogenous T cells when bound to the CD19-expressing target cell. This is the first time that in vivo autologous T-cells have been utilized rather than allogeneic T-cells to treat ALL, notes Douer.
Blinatumomab is administered as a continuous infusion. The overall toxicity is relatively low, states Douer. However, the cytokines released by the activated T cells can result in cytokine release syndrome, which usually presents as fevers, hypoxia, and decreases in blood pressure. Because these adverse events typically occur in the early stages of therapy, the first days of treatment with blinatumomab should be given in the hospital. Neurotoxicity can also present later during treatment, although it is less common. Steroids may be used to treat adverse events.
Once patients on blinatumomab therapy transition to outpatient administration, they must return to clinic every other day to change the infusion bag, says Douer. While this therapy is not a curable approach, it does allow patients more time to get the only curable treatment, which is allogeneic transplant. As a result, Douer recommends using blinatumomab early, for those with refractory disease.