Predictive Factors of Treatment Response to Hypomethylating Agents in Patients with Myelodysplastic Syndrome

Background: Hypomethylating agents (HMAs), including decitabine and azacitidine, have improved outcomes for patients with myelodysplastic syndrome (MDS). However, not all patients benefit from this therapy, and no reliable prognostic tool can predict differential likelihood of benefit from HMAs.

Methods: To investigate predictive factors of treatment response to HMAs in patients with MDS, we analyzed the baseline biomarkers, clinical variables and TP53 mutations of 52 newly diagnosed Chinese patients with MDS who received decitabine or azacitidine (1-23 cycles, median number cycles: 7)

Results: In the 46 assessable patients who received more than 2 cycles of standard treatment, a total of 22 patients had an overall response after treatment, and 24 patents showed no response. The results showed that there was no significant difference in response by treatment regimen (P=0.147) or source of sample (P=0.413). Furthermore, age (P=0.382), sex (P=0.595), IPSS risk groups (P=0.117) and cytogenetic abnormalities (P=0.935) were not associated with response rate. However, in univariate analysis of the overall cohort (n=40) who received more than 3 cycles of standard treatment, the response rate was significantly higher for those patients who had platelet count doubling after 2 cycle of treatment (P=0.013), but there was no statistically difference after 1 cycle(P=0.376). Moreover, a total of 5 patients (11%) had TP53 mutations, overall response rate to HMAs was 100% in patients with TP53 mutation, which is significantly higher than that of patients with wild type cases (p = 0.013).

Conclusions: These findings indicate that patients with TP53 mutation or achieving platelet count doubling after 2 cycle of HMAs respond well.