Venetoclax plus hypomethylating agents in DDX41-mutated acute myeloid leukaemia and myelodysplastic syndrome: Mayo Clinic series on 12 patients

Br J Haematol. 2024 Jan;204(1):171-176. doi: 10.1111/bjh.19105. Epub 2023 Sep 14.

Abstract

Venetoclax (VEN) is an FDA-approved selective inhibitor of B-cell leukaemia/lymphoma-2 (BCL-2), used for treating elderly or unfit acute myeloid leukaemia (AML) patients unable to undergo intensive chemotherapy. Combining VEN with hypomethylating agents (HMAs) has shown impressive response rates in high-risk myelodysplastic syndromes (MDS) and relapsed/refractory AML. However, the efficacy of VEN and HMAs in treating DDX41-mutated (mDDX41) MDS/AML patients remains uncertain. Despite the favourable prognostic nature of mDDX41 MDS/AML patients, there is a lack of clinical experience regarding their response to different treatment regimens, leading to an unknown optimal therapeutic approach.

Keywords: DDX41; hypomethylating agents; response; treatment; venetoclax.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic
  • DEAD-box RNA Helicases
  • Humans
  • Leukemia, Myeloid, Acute* / chemically induced
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Myelodysplastic Syndromes* / chemically induced
  • Myelodysplastic Syndromes* / drug therapy
  • Myelodysplastic Syndromes* / genetics
  • Sulfonamides

Substances

  • venetoclax
  • Bridged Bicyclo Compounds, Heterocyclic
  • Sulfonamides
  • DDX41 protein, human
  • DEAD-box RNA Helicases