Continued decitabine/all-trans retinoic acid treatment: extended complete remission in an elderly AML patient with multi-hit TP53 lesions and complex-monosomal karyotype

Clin Epigenetics. 2024 Sep 11;16(1):126. doi: 10.1186/s13148-024-01737-4.

Abstract

DNA-hypomethylating agents (HMAs) induce notable remission rates in AML/MDS patients with TP53 mutations; however, secondary resistance often develops rapidly. In the DECIDER trial (NCT00867672), elderly AML patients (also those with adverse genetics) randomized to all-trans retinoic acid (ATRA) added to decitabine (DEC) attained significantly delayed time-to-resistance. An 82-year-old patient with a non-disruptive, in-frame TP53 mutation (p.Cys238_Asn239delinsTyr, VAF 90%) and complex-monosomal karyotype attained a complete hematologic and cytogenetic remission with DEC + ATRA, with 3.7 years survival after 30 treatment cycles that were well-tolerated. Further HMA + ATRA studies appear warranted in AML/MDS patients of different genetic risk groups ineligible for more intensive treatment.Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT00867672.

Publication types

  • Case Reports

MeSH terms

  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Decitabine* / administration & dosage
  • Decitabine* / therapeutic use
  • Female
  • Humans
  • Karyotype
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Male
  • Mutation
  • Remission Induction* / methods
  • Tretinoin* / therapeutic use
  • Tumor Suppressor Protein p53* / genetics

Substances

  • Decitabine
  • Tretinoin
  • Tumor Suppressor Protein p53
  • TP53 protein, human

Associated data

  • ClinicalTrials.gov/NCT00867672