Treatment intensification with FLAG-Ida may improve disease control in younger patients with secondary acute myeloid leukaemia: long-term follow up of the MRC AML15 trial

Br J Haematol. 2022 Mar;196(6):1344-1347. doi: 10.1111/bjh.17974. Epub 2021 Dec 13.

Abstract

Secondary acute myeloid leukaemia (AML) has a poor outcome following "3 + 7-like" chemotherapy. While CPX-351 has been approved for patients aged 60-75, the optimal treatment, or comparator, in younger patients is less clear. The MRC AML15 trial randomised younger patients between daunorubicin and ara-C (DA) and DA plus etoposide (ADE) and ADE and fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-Ida) induction. Overall results failed to show an overall survival benefit for FLAG-Ida despite a reduction in relapse, the outcome of patients <60 years with secondary AML compared to DA/ADE was not reported. In this group (n = 115) response to induction was not different [complete remission/complete remission with incomplete haematological response 81% vs. 79%), however, 5-year overall survival and relapse free survival was superior for FLAG-Ida [37% vs. 27%, stratified hazard ratio (HR) 0·45 (0·33-0·90) P = 0·02 and 41% vs. 22%; stratified HR 0·54 (0·31-0·96) P = 0·04] respectively, suggesting that younger patients with secondary AML may benefit from treatment intensification and that "3 + 7" may not be the optimal comparator in trials for this group of patients.

Keywords: chemotherapy; clinical trial; secondary acute myeloid leukaemia.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Cytarabine
  • Follow-Up Studies
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Idarubicin* / therapeutic use
  • Leukemia, Myeloid, Acute* / drug therapy
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasms, Second Primary* / drug therapy
  • Remission Induction
  • Vidarabine

Substances

  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Vidarabine
  • Idarubicin