Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17)

J Clin Oncol. 2013 Dec 10;31(35):4424-30. doi: 10.1200/JCO.2013.49.0771. Epub 2013 Oct 14.

Abstract

Purpose: This randomized trial evaluated the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia (AML).

Patients and methods: Patients (n = 472) age 61 to 75 years were randomly assigned to induction chemotherapy with mitoxantrone, cytarabine, and etoposide preceded, or not, by a course of GO (6 mg/m(2) on days 1 and 15). In remission, patients received two consolidation courses with or without GO (3 mg/m(2) on day 0). The primary end point was overall survival (OS).

Results: The overall response rate was comparable between the two arms (GO, 45%; no GO, 49%), but induction and 60-day mortality rates were higher in the GO arm (17% v 12% and 22% v 18%, respectively). With median follow-up of 5.2 years, median OS was 7.1 months in the GO arm and 10 months in the no-GO arm (hazard ratio, 1.20; 95% CI, 0.99 to 1.45; P = .07). Other survival end points were similar in both arms. Grade 3 to 4 hematologic and liver toxicities were greater in the GO arm. Treatment with GO provided no benefit in any prognostic subgroup, with the possible exception of patients age < 70 years with secondary AML, but outcomes were significantly worse in the oldest age subgroup because of a higher risk of early mortality.

Conclusion: As used in this trial, the sequential combination of GO and standard chemotherapy provides no benefit for older patients with AML and is too toxic for those age ≥ 70 years.

Trial registration: ClinicalTrials.gov NCT00052299.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Aminoglycosides / administration & dosage
  • Aminoglycosides / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Febrile Neutropenia / chemically induced
  • Female
  • Follow-Up Studies
  • Gemtuzumab
  • Humans
  • Induction Chemotherapy / methods
  • Infections / chemically induced
  • Leukemia, Myeloid / diagnosis
  • Leukemia, Myeloid / drug therapy*
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Mitoxantrone / adverse effects
  • Remission Induction
  • Survival Analysis
  • Treatment Outcome

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal, Humanized
  • Cytarabine
  • Etoposide
  • Gemtuzumab
  • Mitoxantrone

Associated data

  • ClinicalTrials.gov/NCT00052299