Efficacy outcomes in the treatment of older or medically unfit patients with acute myeloid leukaemia: A systematic review and meta-analysis

Leuk Res. 2019 Jul:82:36-42. doi: 10.1016/j.leukres.2019.05.007. Epub 2019 May 21.

Abstract

Older and medically unfit patients with acute myeloid leukaemia (AML) who are unsuitable for standard induction therapy have limited treatment options. A meta-analysis was performed with two objectives: 1) to describe outcomes for patients treated with hypomethylating agents, either decitabine or azacitidine, or low-dose cytarabine (LDAC) and 2) to describe the effect of age (<75 vs ≥75) on the remission rates. Thirteen published multi-centre studies in 1822 patients were identified where patients were treated with hypomethylating agents or LDAC. A random effects meta-analysis was performed to provide a pooled estimate of efficacy for the following endpoints: complete remission (CR), overall response rate (CR + complete remission with incomplete white blood cell recovery [CRi]), relapse free survival (RFS), overall survival (OS), and 60-day mortality. For all endpoints apart from RFS, there was significant unexplained between-trial variability (I2 > 64%). The pooled estimates of average outcome across studies were 15% (95% CI: 12%-19%) for CR; 22% (95% CI: 18%-26%) for overall response rate; 8.8 months (95% CI: 7.7 m-10.0 m) for median RFS; 6.3 months (95% CI: 5.3 m-7.4 m) for median OS and 21% (95% CI: 18%-25%) for 60-day mortality. The odds of response were 1.85 times higher (95% CI: 1.3-2.7) among patients who were <75 compared to those who were older.

Keywords: Acute myeloid leukemia; Hypomethylating agents; Low-Dose cytarabine; Meta-Analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Age Factors
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Azacitidine / therapeutic use*
  • Cytarabine / therapeutic use*
  • Decitabine / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Remission Induction
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Cytarabine
  • Decitabine
  • Azacitidine