Outcomes of relapsed or refractory acute myeloid leukemia patients failing venetoclax-based salvage therapies

Eur J Haematol. 2021 Jan;106(1):105-113. doi: 10.1111/ejh.13527. Epub 2020 Oct 27.

Abstract

Objectives and methods: We conducted a retrospective analysis to evaluate the outcomes of 28 heavily pretreated (median 3 (2-6) treatment lines, sixteen (57%) allotransplanted) relapsed/refractory acute myeloid leukemia patients who had failed salvage venetoclax-based therapies.

Results: The median age was 59 years (20-80), 20 patients (71%) had ECOG 2-4 status, and 18 patients (64%) were stratified to European Leukemia Network 2017 adverse risk group. The most common mutations were ASXL1 (21%), RUNX1 (18%), FLT3 ITD/TKD (18%), PTPN11 (15%), NRAS/KRAS (15%), and WT1 (15%). Twenty-two patients (79%) received different post-venetoclax salvage therapies with the overall response rate of 23% (complete remission + morphological leukemia-free state). Three of six (50%) patients achieved complete remissions after therapy with venetoclax + actinomycin D ± low-dose cytarabine. The remaining 6 patients did not receive any further salvage treatment mainly due to poor general condition. The median overall survival was 3.9 months for all patients (4.3 for those receiving post-venetoclax salvage vs 1.3 months receiving palliative care alone, P < .001).

Conclusions: Though the remission rate and survival of patients failing venetoclax are poor, a small proportion of these R/R AML patients may still respond to cautious intensification of chemotherapy with venetoclax.

Keywords: acute myeloid leukemia.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bridged Bicyclo Compounds, Heterocyclic / administration & dosage
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / mortality*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Recurrence
  • Salvage Therapy
  • Sulfonamides / administration & dosage
  • Treatment Failure
  • Young Adult

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Sulfonamides
  • venetoclax