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Blinatumomab approved to treat ALL in Japan

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%).

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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%).

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%).

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