A French study published Online First in The Lancet has revealed that fractionizing the dosage of the targeted anticancer drug gemtuzumab ozogamicin allows for safer delivery of the drug into patients between the ages of 50 to 70 years with acute myeloid leukemia (AML) and significantly improves their outcomes.

Earlier research has demonstrated that although gemtuzumab ozogamicin can cause AML to go into remission, the dosing regimen meant frequent reports of complications, such as liver toxicity and veno-occlusive disease.

Professor Sylvie Castaigne, at the Centre Hospitalier de Versailles, France, and her team decided to examine in their study whether adding a low fractionated-dose of gemtuzumab ozogamicin to standard front-line chemotherapy would improve the outcome of patients with AML without causing excessive toxicity.

They conducted a phase 3 randomized trial in 26 French hematology centers involving 280 patients between the ages of 50 to 70 years with previously untreated primary acute myeloid leukemia. 140 participants were randomly assigned to receive standard therapy (control group) in a 1:1 ratio with and 140 patients without five doses of intravenous gemtuzumab ozogamicin, administered as 3 mg/m² on days 1, 4, and 7 during induction and day 1 of each of the two consolidation chemotherapy courses. The primary endpoint was determined as event-free survival (EFS), with secondary endpoints determined as relapse-free survival (RFS), overall survival (OS) and safety and in each group 139 patients were assessed.

The findings revealed a complete response with or without incomplete platelet recovery to induction of 104 or 75% of participants in the control group and 113 or 81% participants in the gemtuzumab ozogamicin group. At the 2-year primary endpoint, the estimated EFS was 17% in the control group compared with 41% in the gemtuzumab ozogamicin group. The secondary endpoints in the control group revealed an OS of 42%, relapse free survival of 23% compared to an OS of 53% and FRS of 50% in the gemtuzumab ozogamicin group.

The outcome showed that 16% in the gemtuzumab ozogamicin group displayed hematological toxicity, in particular persistent thrombocytopenia, compared with only 3% in the control group without increased risk of death from toxicity.

The researchers conclude:

“The results of this study show that the addition of fractionated doses of gemtuzumab ozogamicin to standard chemotherapy improves the survival outcome in patients aged 50-70 years with de novo acute myeloid leukemia. The regimen [used in this study] allows the delivery of a high cumulative dose of gemtuzumab ozogamicin without excess toxicity.

We believe that our results support the reevaluation of the place of gemtuzumab ozogamicin in available front-line therapy for acute myeloid leukemia. The substantial benefit of adding gemtuzumab ozagamicin is noted not only in patients with acute myeloid leukemia who have favorable cytogenetics, but also in the larger subpopulation of those with intermediate cytogenetics.”

Dr Elihu Estey, University of Washington Medical Center, Seattle, WA, USA; and Fred Hutchinson Cancer Research Center, Seattle, WA, USA, writes in an associated comment:

“Should gemtuzumab ozogamicin be approved for treatment of acute myeloid leukemia? The data suggest a nuanced response. Approval seems warranted for patients with acute promyelocytic leukemia and, in combination with chemotherapy, for patients with favorable or intermediate risk cytogenetics, irrespective of age; in the best-case scenario, cytogenetics might be used predictively. Indeed, experience with gemtuzumab ozogamicin suggests a need to move beyond focusing on an average result. Instead, emphasis needs to be placed on outcome in various subsets of this highly heterogeneous disease.”

Written by Petra Rattue