title: Differential response to hypomethylating agents based on sex: a report on behalf of the MDS Clinical Research Consortium (MDS CRC).
abstract: First-line therapy for higher-risk myelodysplastic syndromes (MDS) includes decitabine (DAC) or azacitidine (AZA). Variables have not identified differential response rates between these. We assessed the influence of patient sex on outcomes including overall survival (OS) in 642 patients with higher-risk MDS treated with AZA or DAC. DAC-treated patients (35% of females, 31% of males) had marginally better OS than AZA-treated patients (p = .043), (median OS of 18.7 months versus 16.4 months), but the difference varied strongly by sex. Female patients treated with DAC had a longer median OS (21.1 months, 95% CI: 16.0-28.0) than female patients treated with AZA (13.2 months, 95% CI: 11.0-15.9; p = .0014), while for males there was no significant difference between HMAs (median OS 18.3 months with DAC versus 17.9 months for AZA, p = .59). The biological reason for this variability is unclear, but may be a consequence of differences in cytidine deaminase activity between men and women.
authors: a Department of Oncology , Sidney Kimmel Cancer Center , Baltimore , MD , USA.
authors: Amy E
authors: AE
authors: DeZern
authors: b Yale Cancer Center, Yale University , New Haven , CT , USA.
authors: Amer M
authors: AM
authors: Zeidan
authors: c Leukemia Program, Cleveland Clinic Taussig Cancer Institute , Cleveland , OH , USA.
authors: John
authors: J
authors: Barnard
authors: a Department of Oncology , Sidney Kimmel Cancer Center , Baltimore , MD , USA.
authors: Wesley
authors: W
authors: Hand
authors: d Hematologic Malignancies, H. Lee Moffitt Cancer Center , Tampa , FL , USA.
authors: Najla
authors: N
authors: Al Ali
authors: e Adult Leukemia Program, Department of Medical Oncology , Dana-Farber Cancer Institute , Boston , MA , USA.
authors: Francis
authors: F
authors: Brown
authors: c Leukemia Program, Cleveland Clinic Taussig Cancer Institute , Cleveland , OH , USA.
authors: Cassie
authors: C
authors: Zimmerman
authors: f Weill Medical College of Cornell University, Leukemia Program , New York , NY , USA.
authors: Gail J
authors: GJ
authors: Roboz
authors: g MD Anderson Comprehensive Cancer Center , Houston , TX , USA.
authors: Guillermo
authors: G
authors: Garcia-Manero
authors: e Adult Leukemia Program, Department of Medical Oncology , Dana-Farber Cancer Institute , Boston , MA , USA.
authors: David P
authors: DP
authors: Steensma
authors: d Hematologic Malignancies, H. Lee Moffitt Cancer Center , Tampa , FL , USA.
authors: Rami S
authors: RS
authors: Komrokji
authors: c Leukemia Program, Cleveland Clinic Taussig Cancer Institute , Cleveland , OH , USA.
authors: Mikkael A
authors: MA
authors: Sekeres
mesh_terms: D000328:Adult; 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; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine
keywords: MDS; Sex; azacitidine; decitabine; hypomethylating agents