title: Discontinuation of hypomethylating agent therapy in patients with myelodysplastic syndromes or acute myelogenous leukemia in complete remission or partial response: retrospective analysis of survival after long-term follow-up.
abstract: Hypomethylating agents (HMA), such as 5-azacitidine or decitabine, are currently used to treat patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) until treatment failure. However, the outcomes for patients who discontinue therapy after achieving partial response (PR) or complete remission (CR) but before treatment failure have not been reported. We present a series of 16 patients with higher-risk MDS (n=5; 31%) or AML (n=11; 69%) who achieved PR (n=1) or CR (n=15) and stopped HMA therapy while in response in the context of clinical trials. They received a median of 12 courses (range 1-24) and achieved response after a median of 1 course of therapy (1-4). Loss of response after discontinuation of therapy was rapid, with a median progression-free survival of 4 months (95% CI: 2-6). Median overall survival (OS) from the time of therapy discontinuation was 15 months (95% CI: 6-24). Patients who received 12 cycles of therapy or more had significantly better OS (median: 20 months [95% CI: 12-27]) than those who received fewer than 12 cycles (median: 4 months [95% CI: 1-8]) (p=0.043). Poor-risk cytogenetics were also associated with lower 1-year OS (33% versus 69%; p=0.046). According to these results and considering the poor prognosis after HMA failure, HMA interruption should be avoided once a sustained response has been achieved.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Monica
authors.initials: M
authors.lastname: Cabrero
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Zach
authors.initials: Z
authors.lastname: Bohannan
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. Electronic address: ggarciam@mdanderson.org.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality*; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D028761:Withholding Treatment / Q000706:statistics & numerical data*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine
keywords: Hypomethylating agents; Myelodysplastic syndromes; Treatment discontinuation
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