Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL-2 and/or BIM

Eur J Haematol. 2019 May;102(5):437-441. doi: 10.1111/ejh.13218. Epub 2019 Feb 28.


Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL-2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL-2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non-responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.

Keywords: BCL-2; BIM; IDH1; IDH2; MCL-1; azacitidine; hypomethylating agents; myeloproliferative neoplasm; secondary acute myeloid leukemia; venetoclax.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Bcl-2-Like Protein 11 / genetics*
  • Bcl-2-Like Protein 11 / metabolism
  • Biomarkers, Tumor
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use*
  • DNA Methylation / drug effects
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Remission Induction
  • Retreatment
  • Sulfonamides / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents
  • BCL2 protein, human
  • Bcl-2-Like Protein 11
  • Biomarkers, Tumor
  • Bridged Bicyclo Compounds, Heterocyclic
  • Proto-Oncogene Proteins c-bcl-2
  • Sulfonamides
  • venetoclax