FLT3

Comparison of anthracyclines used for induction chemotherapy in patients with FLT3-ITD mutated AML

In the March issue of Leukemia Research, Eun-Ji Choi from Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, and colleagues published results of their retrospective analysis examining the clinical impact of different types and doses of anthracyclines as a part of induction regimen for the treatment of newly diagnosed FLT3-ITD mutated acute myeloid leukemia (AML) patients. Study endpoints included the response to induction treatment, relapse, and survival rates.

In total, 128 adult patients with AML harboring FLT3-ITD mutations who received one of three induction regimens at the Asan Medical Center between January 2002 and September 2016 were included in this analysis. Patients were administered induction regimens consisting of either high-dose daunorubicin (HD-DN; 90 mg/m2/d for 3 days, n = 44), standard-dose daunorubicin (SD-DN; 45 mg/m2/d for 3 days; n = 51), or idarubicin (IDA; 12 mg/ m2/d for 3 days; n = 33) in combination with cytarabine (100 or 200 mg/m2/d for 7 days).

Key findings:

Complete remission (CR) rates:

  • Overall CR rate for all patients: 67.2% (after one or two courses of induction therapy)
  • Overall CR rates in the HD-DN, SD-DN and IDA groups were 77.3% vs 56.9% vs 69.7%, P = 0.101
    • Overall CR rates were significantly different between the HD-DN and SD-DN groups, P = 0.036
    • Overall CR rates was not significantly different between the HD-DN vs IDA, P = 0.453
    • Overall CR rates was not significantly different between the IDA vs SD-DN, P = 0.237

Survival rates:

  • Median follow-up: 70.6 months (95% CI, 61.9–79.3)
  • 5-year OS for all patients: 35.9%
  • 5-year EFS for all patients: 29.1%
  • 5-year cumulative incidence of relapse (CIR) for all patients: 60.0%
  • OS was significantly different in the HD-DN and SD-DN groups, P = 0.009
  • EFS was significantly different in the HD-DN and SD-DN groups, P = 0.010

In vitro comparison of daunorubicin vs IDA using six FLT3-ITD-mutated AML cell lines after 24h of exposure

  • 100 nM daunorubicin showed significantly greater inhibitory effects than 50 nM daunorubicin
  • 20 nM IDA was not significantly different than 10 nM IDA

In summary, compared with SD-DN, HD-DN improved CR, OS, and EFS in FLT3-ITD-mutated AML patients. In vitro examination of FLT3-ITD-mutated cell lines confirmed these findings. Moreover, HD-DN showed superior outcomes than IDA, nevertheless the difference was not significantly different. The study group further added that “optimal combinations of FLT3 inhibitors and effective intensive chemotherapy regimens should be defined.” The advantage of HD-DN versus IDA requires further investigation.

References
  1. Choi E.J. et al. Comparison of anthracyclines used for induction chemotherapy in patients with FLT3-ITD-mutated acute myeloid leukemia. Leukemia Research. 2018 March 8. DOI: 10.1016/j.leukres.2018.03.006. [Epub ahead of print].