Efficacy and Safety of Low-Dose Decitabine in Low- or Intermediate 1-Risk MDS

OBJECTIVES: Decitabine has been approved in China for treatment with high-risk Myelodysplastic syndromes (MDS) patients (pts) in 2008. However data of decitabine on efficacy and safety of low-dose decitabine in low- or intermediate 1-risk MDS was absence. Herein,3 years datas in our centre of low- or intermediate 1-risk MDS treated with decitabine were analysed to evaluate the efficacy and safety in two subgroups.

METHODS: Inclusion Criteria:Patients of age > 18; Patients with low-or intermediate 1-risk MDS. The IPSS is used to classify patients with MDS across disease subgroups. ECOG performance status ≤ 2. And normal hepatic,renal and cardiac function. Study Design: Decitabine 20mg/m2 intravenously (IV) over the course of one hour daily for 3 days. Courses were repeated every 28 days when possible. Dose reductions for grade 3 and 4 toxicities were allowed for decitabine (to 10 mg/m2 or 15 mg/m2). The primary endpoint was overall response rate (ORR).

RESULTS: In total, 37 patients were enrolled and treated from September 2014 to October 2017 in our center. The median follow-up was 26 months (range, 4-49 months). The median time from diagnosis to therapy with decitabine was 3 weeks (range, 1-52 weeks). Their F/M ratio was 16/21 and the median age of the enrolled population was 58 years (range, 40-71 years). More than 70% of patients had 2 to 3 cytopenias, and 43% were transfusion dependent at enrollment. Most patients had intermediate 1-risk MDS by IPSS (n=29). Next-generation sequencing was performed in 35 patients (90%). The most frequently detected mutations included TET2 (n=15; 41%), SF3B1 (n=7; 19%), ASXL1 (n=5, 13%), RUNX1 (n= 5, 13%), and SRSF2 (n=3, 8%). The ORR after 2 cycles of decitabine was 65% (24/37),with 35% of patients (13/35) achieving a CR. Hematologic improvement was seen in 19%(7/37). The median time to best response was 3 months (range, 1-12 months). The median number of cycles received was 5 (range, 1-13 cycles). 19% of patients (7/37) became transfusion independent. The EFS and OS were 68% and 78% respectively in 1 year. The treatment was well-tolerated, with most adverse events being of grade 1 to 2, Nausea (24%), Fatigue (14%), Infection/Neutropenic fever (19%), Constipation (6%), Diarrhea (6%). Grade 3 and higher nonhematologic adverse events were rare. Grade 3 adverse events were Infection/Neutropenic fever (6%), but rare, and no grade 4 adverse events were observed.

CONCLUSIONS: These data confirm that decitabine is a feasible and effective agent for low- or intermediate 1-risk MDS pts, and its need longer time to response (more than 2 cycles). Safety profile was acceptable and the most adverse events were Nausea, Fatigue, and Infection/Neutropenic fever.