Olutasidenib in post-venetoclax patients with mutant isocitrate dehydrogenase 1 (m IDH1) acute myeloid leukemia (AML)

Leuk Lymphoma. 2024 Aug;65(8):1145-1152. doi: 10.1080/10428194.2024.2333451. Epub 2024 Mar 27.

Abstract

Olutasidenib, a potent, selective, oral, mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor, is FDA-approved for relapsed/refractory (R/R) acute myeloid leukemia (AML). Here we report efficacy and safety of olutasidenib in 18 patients with mIDH1 AML who were relapsed (10), refractory (6) or had complete remission with incomplete hematologic recovery (CRi; 2) to a venetoclax combination. Of the 16 patients who were R/R, 4 (25%) achieved complete remission (CR), one (6.3%) achieved CR with partial hematologic recovery (CRh), and 7 (43.8%) achieved a composite complete remission (CRc). Median time to CRc was 1.9 months (range 1-2.8). As of data cutoff (18 June 2021), median duration of CRc was not reached (range, 1.2-NR, ongoing at 30.4+ months). Both patients with CRi at study entry achieved a CR. Safety was consistent with the overall profile of olutasidenib. Olutasidenib offers a valuable treatment option for patients with mIDH1 AML previously treated with venetoclax.

Keywords: IDH1 mutation; Olutasidenib; acute myeloid leukemia.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic* / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • Isocitrate Dehydrogenase* / antagonists & inhibitors
  • Isocitrate Dehydrogenase* / genetics
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use
  • Remission Induction
  • Sulfonamides* / adverse effects
  • Sulfonamides* / therapeutic use
  • Treatment Outcome

Substances

  • Isocitrate Dehydrogenase
  • Bridged Bicyclo Compounds, Heterocyclic
  • Sulfonamides
  • venetoclax
  • Pyridines
  • IDH1 protein, human
  • Antineoplastic Agents