Photo courtesy of Amgen
Vials of blinatumomab powder and solution for infusion
The Japanese Ministry of Health, Labour and Welfare has approved blinatumomab (Blincyto®) for the treatment of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).
Blinatumomab is the first and only bispecific T-cell engager immunotherapy construct approved globally.
The drug’s approval in Japan is based on data from the phase 3 TOWER study and the phase 1b/2 Horai study.
The TOWER trial (NCT02013167) enrolled 405 patients with Ph-negative, relapsed/refractory B-ALL, 376 of whom ultimately received treatment.
The patients received blinatumomab (n=267) or investigator’s choice of four protocol-defined standard of care (SOC) chemotherapy regimens (n=109):
- FLAG (fludarabine, high-dose cytarabine arabinoside, and granulocyte-colony stimulating factor), with or without an anthracycline (n=49, 45%)
- A high-dose cytarabine arabinoside-based regimen (n=19, 17%)
- A high-dose methotrexate-based regimen (n=22, 20%)
- A clofarabine-based regimen (n=19, 17%).
Blinatumomab demonstrated an improvement in median overall survival over SOC. The median overall survival was 7.7 months with blinatumomab and 4.0 months with SOC (hazard ratio for death=0.71; P=0.012).
Grade 3 or higher adverse events (AEs) of interest, according to the researchers, were:
- Infection (34% with blinatumomab and 52% with chemotherapy)
- Neutropenia (38% and 58%, respectively)
- Elevated liver enzymes (13% and 15%, respectively)
- Neurologic events (9% and 8%, respectively)
- Cytokine release syndrome (5% and 0%, respectively)
- Infusion reactions (3% and 1%, respectively)
- Lymphopenia (2% and 4%, respectively).
Fatal AEs occurred in 19% of patients in the blinatumomab arm and 17% of those in the SOC arm.
These results were published in The New England Journal of Medicine last year.
Horai
For this single-arm trial (NCT02412306), researchers evaluated blinatumomab in 35 Japanese adult and pediatric patients with relapsed or refractory B-ALL. An extension of this study is ongoing.
Efficacy data from Horai are not available.
According to Amgen, the major AEs occurring in adults on this trial were cytokine release syndrome (46.2%), pyrexia (46.2%), decrease in white blood cell count (38.5%), and decrease in platelet count (34.6%).
Major AEs in pediatric patients were elevated liver enzymes (66.7%), pyrexia (66.7%), cytokine release syndrome (55.6%), and abdominal pain (44.4%).