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

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

Johanna Thomas  1 , Usama-Ur Rehman  1 , Helena Bresser  1 , Olga Grishina  2 , Dietmar Pfeifer  1 , Etienne Sollier  3 , Konstanze Döhner  4 , Christoph Plass  3 , Heiko Becker  1   5 , Claudia Schmoor  2 , Maike de Wit  6 , Michael Lübbert  7   8
Affiliations
Case Reports

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

Johanna Thomas et al. Clin Epigenetics. .

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.

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Conflict of interest statement

KD: Consultancy with honoraria: AbbVie, Janssen, Jazz, Novartis, Bristol Myers Squibb, Celgene; Clinical Research Funding to Institution: Novartis, AbbVie, Astellas, Bristol Myers Squibb, Celgene, Jazz Pharmaceuticals, Kronos Bio, Servier and ML: Advisory role with honoraria from AbbVie, Astex Pharmaceuticals, Imago BioSciences, Janssen, Otsuka, Syros. Research support (to institution) from Janssen; clinical research support with study drug from Cheplapharm. The DECIDER study was approved by the central ethics committee (University of Freiburg). The patient’s written consent to participate in this clinical trial was obtained before any study-specific procedures occurred.

Figures

Fig. 1
Fig. 1
A Left panel: BM aspirate at diagnosis of AML (Jan. 2014) shows a dense blast infiltration, right panel: response to DEC + ATRA (October 2014); BM blast percentage 1%. B Circos plot showing copy-number alterations in BM cells obtained prior to treatment start, with losses in blue, gains in red, and diploid regions in black, and the structural variants (SVs) as green arcs observed in WGS data. C Schematic representation of clinical course; kinetics of Hb (black line), BM blast percentage in orange, and leukocyte kinetics in purple. Complex, monosomal karyotype at diagnosis (Jan. 2014), normal karyotype (July 2014); CR from May 2014 to July 2017 (8% BM blast). Therapy administered every 4 weeks (= one cycle), cycle 23–25, therapy administered without ATRA. Timeframe over 3.7 years from therapy initiation with DEC + ATRA until patient decided to stop treatment. Hb hemoglobin; DEC decitabine; ATRA all-trans retinoic acid; BM bone marrow; and CR complete remission
See this image and copyright information in PMC

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