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.

Keywords:

• Sex
• hypomethylating agents
• MDS
• azacitidine
• decitabine

Acknowledgements

We would like to thank the patients who contributed to this large database and their families, as well the research coordinators in the six sites who worked to construct the database. The authors would also like to thank the Edward P. Evans Foundation and the Aplastic Anemia and Myelodysplastic Syndromes Foundation for supporting the research activities of the MDS Clinical Research Consortium. This research was presented in part at the American Society of Hematology 57th Annual meeting in Orlando, FL, USA in December 2015.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1246726.