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The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for gemtuzumab ozogamicin (GO, Mylotarg™).
The recommendation is for GO to be used in combination with daunorubicin and cytarabine to treat patients age 15 years and older with previously untreated, de novo, CD33-positive acute myeloid leukemia (AML) but not acute promyelocytic leukemia.
The CHMP’s opinion on GO will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
Previous rejection
The CHMP previously issued a negative opinion of GO (first in 2007, confirmed in 2008), saying the drug should not receive marketing authorization.
The proposed indication for GO at that time was as re-induction treatment in adults with CD33-positive AML in first relapse who were not candidates for other intensive re-induction chemotherapy regimens and were either older than 60 or had a duration of first remission lasting less than 12 months.
The CHMP said there was insufficient evidence to establish the effectiveness of GO in AML, and the drug’s benefits did not outweigh its risks.
Phase 3 trial
The current marketing authorization application for GO is supported by data from an investigator-led, phase 3, randomized trial known as ALFA-0701. Updated results from this trial are available in the US prescribing information for GO.
Patients and treatment
ALFA-0701 included 271 patients with newly diagnosed, de novo AML who were 50 to 70 years of age.
Patients were randomized (1:1) to receive induction consisting of daunorubicin (60 mg/m2 on days 1 to 3) and cytarabine (200 mg/m2 on days 1 to 7) with (n=135) or without (n=136) GO at 3 mg/m2 (up to maximum of 1 vial) on days 1, 4, and 7. Patients who did not achieve a response after first induction could receive a second induction with daunorubicin and cytarabine alone.
Patients with a response received consolidation therapy with 2 courses of treatment including daunorubicin (60 mg/m2 on day 1 of first consolidation course; 60 mg/m2 on days 1 and 2 of second consolidation course) and cytarabine (1 g/m2 every 12 hours on days 1 to 4) with or without GO at 3 mg/m2 (up to a maximum of 1 vial) on day 1 according to their initial randomization.
Patients who achieved remission were also eligible for allogeneic transplant. An interval of at least 2 months between the last dose of GO and transplant was recommended.
Baseline characteristics were largely well balanced between the treatment arms, but there was a higher percentage of males in the GO arm than the control arm—55% and 44%, respectively.
Results
The study’s primary endpoint was event-free survival. The median event-free survival was 17.3 months in the GO arm and 9.5 months in the control arm (hazard ratio=0.56; 95% CI: 0.42-0.76; P<0.001).
There was no significant difference in overall survival between the treatment arms. (Updated overall survival data have not been provided).
All patients in this trial developed severe neutropenia, thrombocytopenia, and anemia. However, the incidence of prolonged, grade 3–4 thrombocytopenia in the absence of active leukemia was higher in the GO arm.
Treatment-emergent adverse events (AEs) considered most important for understanding the safety profile of GO were hemorrhage, veno-occlusive liver disease (VOD), and severe infections.
Treatment discontinuation due to any AE occurred in 31% of patients in the GO arm and 7% of those in the control arm. The most frequent AEs leading to discontinuation for patients on GO were thrombocytopenia (15%), VOD (3%), and septic shock (2%).
Fatal AEs occurred in 8 patients (6%) in the GO arm and 3 (2%) in the control arm. In the GO arm, 3 patients died of VOD, 4 died of hemorrhage-related events, and 1 died of a suspected cardiac cause. All 3 fatal AEs in the control arm were sepsis.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for gemtuzumab ozogamicin (GO, Mylotarg™).
The recommendation is for GO to be used in combination with daunorubicin and cytarabine to treat patients age 15 years and older with previously untreated, de novo, CD33-positive acute myeloid leukemia (AML) but not acute promyelocytic leukemia.
The CHMP’s opinion on GO will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
Previous rejection
The CHMP previously issued a negative opinion of GO (first in 2007, confirmed in 2008), saying the drug should not receive marketing authorization.
The proposed indication for GO at that time was as re-induction treatment in adults with CD33-positive AML in first relapse who were not candidates for other intensive re-induction chemotherapy regimens and were either older than 60 or had a duration of first remission lasting less than 12 months.
The CHMP said there was insufficient evidence to establish the effectiveness of GO in AML, and the drug’s benefits did not outweigh its risks.
Phase 3 trial
The current marketing authorization application for GO is supported by data from an investigator-led, phase 3, randomized trial known as ALFA-0701. Updated results from this trial are available in the US prescribing information for GO.
Patients and treatment
ALFA-0701 included 271 patients with newly diagnosed, de novo AML who were 50 to 70 years of age.
Patients were randomized (1:1) to receive induction consisting of daunorubicin (60 mg/m2 on days 1 to 3) and cytarabine (200 mg/m2 on days 1 to 7) with (n=135) or without (n=136) GO at 3 mg/m2 (up to maximum of 1 vial) on days 1, 4, and 7. Patients who did not achieve a response after first induction could receive a second induction with daunorubicin and cytarabine alone.
Patients with a response received consolidation therapy with 2 courses of treatment including daunorubicin (60 mg/m2 on day 1 of first consolidation course; 60 mg/m2 on days 1 and 2 of second consolidation course) and cytarabine (1 g/m2 every 12 hours on days 1 to 4) with or without GO at 3 mg/m2 (up to a maximum of 1 vial) on day 1 according to their initial randomization.
Patients who achieved remission were also eligible for allogeneic transplant. An interval of at least 2 months between the last dose of GO and transplant was recommended.
Baseline characteristics were largely well balanced between the treatment arms, but there was a higher percentage of males in the GO arm than the control arm—55% and 44%, respectively.
Results
The study’s primary endpoint was event-free survival. The median event-free survival was 17.3 months in the GO arm and 9.5 months in the control arm (hazard ratio=0.56; 95% CI: 0.42-0.76; P<0.001).
There was no significant difference in overall survival between the treatment arms. (Updated overall survival data have not been provided).
All patients in this trial developed severe neutropenia, thrombocytopenia, and anemia. However, the incidence of prolonged, grade 3–4 thrombocytopenia in the absence of active leukemia was higher in the GO arm.
Treatment-emergent adverse events (AEs) considered most important for understanding the safety profile of GO were hemorrhage, veno-occlusive liver disease (VOD), and severe infections.
Treatment discontinuation due to any AE occurred in 31% of patients in the GO arm and 7% of those in the control arm. The most frequent AEs leading to discontinuation for patients on GO were thrombocytopenia (15%), VOD (3%), and septic shock (2%).
Fatal AEs occurred in 8 patients (6%) in the GO arm and 3 (2%) in the control arm. In the GO arm, 3 patients died of VOD, 4 died of hemorrhage-related events, and 1 died of a suspected cardiac cause. All 3 fatal AEs in the control arm were sepsis.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for gemtuzumab ozogamicin (GO, Mylotarg™).
The recommendation is for GO to be used in combination with daunorubicin and cytarabine to treat patients age 15 years and older with previously untreated, de novo, CD33-positive acute myeloid leukemia (AML) but not acute promyelocytic leukemia.
The CHMP’s opinion on GO will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
Previous rejection
The CHMP previously issued a negative opinion of GO (first in 2007, confirmed in 2008), saying the drug should not receive marketing authorization.
The proposed indication for GO at that time was as re-induction treatment in adults with CD33-positive AML in first relapse who were not candidates for other intensive re-induction chemotherapy regimens and were either older than 60 or had a duration of first remission lasting less than 12 months.
The CHMP said there was insufficient evidence to establish the effectiveness of GO in AML, and the drug’s benefits did not outweigh its risks.
Phase 3 trial
The current marketing authorization application for GO is supported by data from an investigator-led, phase 3, randomized trial known as ALFA-0701. Updated results from this trial are available in the US prescribing information for GO.
Patients and treatment
ALFA-0701 included 271 patients with newly diagnosed, de novo AML who were 50 to 70 years of age.
Patients were randomized (1:1) to receive induction consisting of daunorubicin (60 mg/m2 on days 1 to 3) and cytarabine (200 mg/m2 on days 1 to 7) with (n=135) or without (n=136) GO at 3 mg/m2 (up to maximum of 1 vial) on days 1, 4, and 7. Patients who did not achieve a response after first induction could receive a second induction with daunorubicin and cytarabine alone.
Patients with a response received consolidation therapy with 2 courses of treatment including daunorubicin (60 mg/m2 on day 1 of first consolidation course; 60 mg/m2 on days 1 and 2 of second consolidation course) and cytarabine (1 g/m2 every 12 hours on days 1 to 4) with or without GO at 3 mg/m2 (up to a maximum of 1 vial) on day 1 according to their initial randomization.
Patients who achieved remission were also eligible for allogeneic transplant. An interval of at least 2 months between the last dose of GO and transplant was recommended.
Baseline characteristics were largely well balanced between the treatment arms, but there was a higher percentage of males in the GO arm than the control arm—55% and 44%, respectively.
Results
The study’s primary endpoint was event-free survival. The median event-free survival was 17.3 months in the GO arm and 9.5 months in the control arm (hazard ratio=0.56; 95% CI: 0.42-0.76; P<0.001).
There was no significant difference in overall survival between the treatment arms. (Updated overall survival data have not been provided).
All patients in this trial developed severe neutropenia, thrombocytopenia, and anemia. However, the incidence of prolonged, grade 3–4 thrombocytopenia in the absence of active leukemia was higher in the GO arm.
Treatment-emergent adverse events (AEs) considered most important for understanding the safety profile of GO were hemorrhage, veno-occlusive liver disease (VOD), and severe infections.
Treatment discontinuation due to any AE occurred in 31% of patients in the GO arm and 7% of those in the control arm. The most frequent AEs leading to discontinuation for patients on GO were thrombocytopenia (15%), VOD (3%), and septic shock (2%).
Fatal AEs occurred in 8 patients (6%) in the GO arm and 3 (2%) in the control arm. In the GO arm, 3 patients died of VOD, 4 died of hemorrhage-related events, and 1 died of a suspected cardiac cause. All 3 fatal AEs in the control arm were sepsis.