Combination romidepsin and azacitidine therapy is well tolerated and clinically active in adults with high-risk acute myeloid leukaemia ineligible for intensive chemotherapy

Br J Haematol. 2022 Jan;196(2):368-373. doi: 10.1111/bjh.17823. Epub 2021 Sep 6.

Abstract

Azacitidine (AZA) is important in the management of patients with acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. Romidepsin (ROM) is a histone deacetylase inhibitor which synergises with AZA in vitro. The ROMAZA trial established the maximum tolerated dose (MTD) of combined ROM/AZA therapy in patients with AML, as ROM 12 mg/m2 on Days 8 and 15, with AZA 75 mg/m2 administered for 7/28 day cycle. Nine of the 38 (23·7%) patients treated at the MTD were classified as responders by Cycle 6 (best response: complete remission [CR]/incomplete CR n = 7, partial response n = 2). Correlative next-generation sequencing studies demonstrated important insights into therapy resistance.

Keywords: acute myeloid leukaemia; clinical trial; early phase; hypomethylating agent; refractory; relapsed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Azacitidine / administration & dosage
  • Clinical Decision-Making
  • Cytogenetic Analysis
  • Depsipeptides / administration & dosage
  • Disease Management
  • Disease Susceptibility
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / etiology
  • Male
  • Molecular Targeted Therapy
  • Prognosis
  • Treatment Outcome
  • Young Adult

Substances

  • Depsipeptides
  • romidepsin
  • Azacitidine