Fractionated gemtuzumab ozogamicin and standard dose cytarabine produced prolonged second remissions in patients over the age of 55 years with acute myeloid leukemia in late first relapse

Am J Hematol. 2014 Apr;89(4):399-403. doi: 10.1002/ajh.23653. Epub 2014 Mar 7.

Abstract

Gemtuzumab ozogamicin (fGO), a humanized anti-CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥ 6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m², days 1, 4, 7) with standard-dose cytarabine (200 mg/m² /day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty-four patients (median age 68 years) received fGO with cytarabine. Median follow-up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two-year overall survival (OS) was 51% (95% CI: 28-69) and 2 years relapse-free survival (RFS) was 51% (95%CI: 25-72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse.

MeSH terms

  • Aged
  • Aminoglycosides / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Compassionate Use Trials
  • Consolidation Chemotherapy
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Disease-Free Survival
  • Female
  • Filgrastim
  • Gemtuzumab
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Immunophenotyping
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myelomonocytic, Acute / drug therapy
  • Leukemia, Myelomonocytic, Acute / genetics
  • Male
  • Methylprednisolone / administration & dosage
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / prevention & control
  • Nucleophosmin
  • Recombinant Proteins / therapeutic use
  • Remission Induction
  • Salvage Therapy*
  • Thrombocytopenia / blood
  • Thrombocytopenia / chemically induced

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal, Humanized
  • NPM1 protein, human
  • Recombinant Proteins
  • Cytarabine
  • Nucleophosmin
  • Granulocyte Colony-Stimulating Factor
  • Gemtuzumab
  • Filgrastim
  • Methylprednisolone
  • Daunorubicin