Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study

J Clin Oncol. 2020 Feb 20;38(6):623-632. doi: 10.1200/JCO.19.01406. Epub 2019 Dec 18.


Purpose: High CD33 expression in acute myeloid leukemia (AML) with mutated NPM1 provides a rationale for the evaluation of gemtuzumab ozogamicin (GO) in this AML entity. We conducted a randomized trial to evaluate GO in combination with intensive induction and consolidation therapy in NPM1-mutated AML.

Patients and methods: Between May 2010 and September 2017, patients ≥ 18 years old and considered eligible for intensive therapy were randomly assigned up front for induction therapy with idarubicin, cytarabine, etoposide, and all-trans-retinoic acid with or without GO. The early (P = .02) primary end point of event-free survival (EFS) was evaluated 6 months after completion of patient recruitment.

Results: Five hundred eighty-eight patients were randomly assigned (standard arm, n = 296; GO arm, n = 292). EFS in the GO arm was not significantly different compared with that in the standard arm (hazard ratio, 0.83; 95% CI, 0.65 to 1.04; P = .10). The early death rate during induction therapy was 10.3% in the GO arm and 5.7% in the standard arm (P = .05). Causes of death in both arms were mainly infections. The cumulative incidence of relapse (CIR) in patients achieving a complete remission (CR) or CR with incomplete hematologic recovery (CRi) was significantly reduced in the GO arm compared with the standard arm (P = .005), with no difference in the cumulative incidence of death (P = .80). Subgroup analysis revealed a significant beneficial effect of GO in female, younger (≤ 70 years), and FLT3 internal tandem duplication-negative patients with respect to EFS and CIR.

Conclusion: The trial did not meet its early primary end point of EFS, mainly as a result of a higher early death rate in the GO arm. However, in patients achieving CR/CRi after induction therapy, significantly fewer relapses occurred in the GO compared with the standard arm.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Consolidation Chemotherapy / methods
  • Cytarabine / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Gemtuzumab / therapeutic use*
  • Humans
  • Idarubicin / administration & dosage
  • Induction Chemotherapy / methods
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Progression-Free Survival
  • Prospective Studies
  • Tretinoin / administration & dosage
  • Young Adult


  • Antineoplastic Agents, Immunological
  • NPM1 protein, human
  • Nuclear Proteins
  • Cytarabine
  • Nucleophosmin
  • Tretinoin
  • Etoposide
  • Gemtuzumab
  • Idarubicin