Differential response to hypomethylating agents based on sex: a report on behalf of the MDS Clinical Research Consortium (MDS CRC).
DeZern AE, Zeidan AM, Barnard J, Hand W, Al Ali N, Brown F, Zimmerman C, Roboz GJ, Garcia-Manero G, Steensma DP, Komrokji RS, Sekeres MA, Evans MDS Clinical Research Consortium
Leuk Lymphoma 58 1325-1331 06/01/2017
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.Full Text