Durable responses in acute lymphoblastic leukaemia with the use of FLT3 and IDH inhibitors

Br J Haematol. 2024 Apr;204(4):1238-1242. doi: 10.1111/bjh.19250. Epub 2023 Dec 10.

Abstract

Data regarding the use of FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase 1/2 (IDH1/2) inhibitors in acute lymphoblastic leukaemia (ALL) are lacking. We identified 14 patients with FLT3- or IDH1/2-mutated ALL. Three early T-cell precursor-ALL patients received FLT3 or IDH2 inhibitors. Patient 1 maintains a complete remission (CR) with enasidenib after intolerance to chemotherapy. Patient 2 maintained a CR for 27 months after treatment with enasidenib for relapsed disease. Patient 3 was treated with venetoclax and gilteritinib at the time of relapse and maintained a CR with gilteritinib for 8 months. These cases suggest that FLT3 and IDH inhibitors could represent a viable therapeutic option for ALL patients with these mutations.

Keywords: ALL; FLT3; IDH1; IDH2; targeted.

MeSH terms

  • Aminopyridines*
  • Aniline Compounds*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Mutation
  • Neoplasm Recurrence, Local
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Pyrazines*
  • Triazines*
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • gilteritinib
  • enasidenib
  • fms-Like Tyrosine Kinase 3
  • Enzyme Inhibitors
  • FLT3 protein, human
  • Aminopyridines
  • Aniline Compounds
  • Pyrazines
  • Triazines