Outcomes of acute myeloid leukemia patients who responded to venetoclax and azacitidine and stopped treatment

Am J Hematol. 2024 Oct;99(10):1870-1876. doi: 10.1002/ajh.27417. Epub 2024 Jun 20.

Abstract

Venetoclax-azacitidine is the standard of treatment for unfit acute myeloid leukemia patients. In the VIALE-A study, treatment was given until progression but there are no data on its optimal duration for responding patients who do not tolerate indefinite therapy. We retrospectively analyzed the outcome of patients who discontinued venetoclax or venetoclax-azacitidine due to poor tolerance. Sixty-two newly diagnosed (ND) AML patients and 22 patients with morphological relapse or refractory AML were included. In the ND cohort (n = 62), 28 patients stopped venetoclax and azacitidine and 34 patients continued azacitidine monotherapy. With a median follow-up of 23 months (IQR, 20-32), median overall survival and treatment-free survival were 44 (IQR, 16-NR) and 16 (IQR, 8-27) months, respectively. Patients who stopped both treatments and those who continued azacitidine monotherapy had the same outcomes. Negative minimal residual disease was associated with a 2-year treatment-free survival of 80%. In the RR cohort (n = 22), median overall survival and treatment-free survival were 19 (IQR, 17-31) and 10 (IQR, 5-NR) months, respectively. Prior number of venetoclax-azacitidine cycles and IDH mutations were associated with increased overall survival. The only factor significantly impacting treatment-free survival was the number of prior cycles. This study suggests that patients who discontinued treatment in remission have favorable outcomes supporting the rationale for prospective controlled trials.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Azacitidine* / administration & dosage
  • Azacitidine* / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic* / administration & dosage
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Disease-Free Survival
  • Female
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / mortality
  • Male
  • Middle Aged
  • Mutation
  • Retrospective Studies
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / therapeutic use
  • Treatment Outcome
  • Withholding Treatment / statistics & numerical data

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Azacitidine
  • Sulfonamides
  • venetoclax
  • Isocitrate Dehydrogenase