Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG

Ann Hematol. 2018 Apr;97(4):573-584. doi: 10.1007/s00277-017-3217-1. Epub 2017 Dec 29.

Abstract

The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000-45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.

Keywords: Acute myeloid leukemia; Clofarabine; Elderly patients; FLAG; Leukemia.

Publication types

  • Comparative Study

MeSH terms

  • Adenine Nucleotides / adverse effects
  • Adenine Nucleotides / economics
  • Adenine Nucleotides / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Aging*
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / economics
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / economics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arabinonucleosides / adverse effects
  • Arabinonucleosides / economics
  • Arabinonucleosides / therapeutic use*
  • Case-Control Studies
  • Chemical and Drug Induced Liver Injury / economics
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / mortality
  • Chemical and Drug Induced Liver Injury / therapy
  • Clofarabine
  • Cohort Studies
  • Combined Modality Therapy / economics
  • Cost Savings
  • Costs and Cost Analysis
  • Cytarabine / adverse effects
  • Cytarabine / economics
  • Cytarabine / therapeutic use
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / economics
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hospital Costs
  • Humans
  • Incidence
  • Induction Chemotherapy* / adverse effects
  • Induction Chemotherapy* / economics
  • Length of Stay
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / economics
  • Leukemia, Myeloid, Acute / mortality
  • Michigan / epidemiology
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / economics
  • Neutropenia / mortality
  • Neutropenia / therapy
  • Propensity Score
  • Retrospective Studies
  • Survival Analysis
  • Tertiary Care Centers
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives*
  • Vidarabine / economics
  • Vidarabine / therapeutic use

Substances

  • Adenine Nucleotides
  • Antimetabolites, Antineoplastic
  • Arabinonucleosides
  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Clofarabine
  • Vidarabine

Supplementary concepts

  • FLAG protocol