High-dose cytarabine plus gemtuzumab ozogamicin as consolidation therapy in patients with favorable- or intermediate-risk acute myeloid leukemia

Int J Hematol. 2024 Sep;120(3):297-304. doi: 10.1007/s12185-024-03814-z. Epub 2024 Jul 4.

Abstract

Previous prospective randomized trials have investigated the efficacy of gemtuzumab ozogamicin in the frontline treatment of acute myeloid leukemia (AML). We evaluated the efficacy of high-dose cytarabine with GO as consolidation therapy in 20 patients with favorable- or intermediate-risk AML in first complete remission. They included six patients with wild-type nucleophosmin (NPM1) core binding factor (CBF), ten with NPM1-mutated non-CBF, and four with wild-type NPM1 non-CBF. The median follow-up for the entire cohort was 62.0 months. The three-year overall survival (OS) and relapse-free survival (RFS) rates were 72.2% and 77.8%, respectively. OS and RFS were significantly higher for NPM1-mutated non-CBF AML than for wild-type NPM1 non-CBF AML (p = 0.001). We also examined the CD33 single-nucleotide polymorphism (SNP) rs12459419, which has been reported to influence the therapeutic efficacy of GO and CD33 expression. The CD33 expression ratio was higher in CD33 SNP C/C than in C/T (83.1% vs. 49.8%, p = 0.035), but 3-year OS and RFS did not differ significantly. These results suggest that consolidation therapy with high-dose cytarabine plus GO is highly effective in transplant-ineligible elderly patients and may be a reasonable treatment, especially for NPM1-mutated AML.

Keywords: NPM1-mutated AML; Consolidation therapy; Gemtuzumab ozogamicin.

MeSH terms

  • Adult
  • Aged
  • Aminoglycosides* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Consolidation Chemotherapy*
  • Cytarabine* / administration & dosage
  • Female
  • Gemtuzumab* / administration & dosage
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / mortality
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics
  • Nucleophosmin*
  • Polymorphism, Single Nucleotide
  • Sialic Acid Binding Ig-like Lectin 3 / genetics
  • Treatment Outcome

Substances

  • Gemtuzumab
  • Cytarabine
  • Nucleophosmin
  • NPM1 protein, human
  • Aminoglycosides
  • Sialic Acid Binding Ig-like Lectin 3
  • Nuclear Proteins
  • CD33 protein, human