Retrospective Case Series Study of Hypomethylating Therapy in IPSS Lower-Risk Myelodysplastic Syndrome

Introduction: The IPSS has been widely used for risk stratification in myelodysplastic syndromes (MDS), and patients with IPSS low and intermediate-1 scores are designated as having lower-risk (LR) MDS. Despite its utility, the outcomes of patients with LR disease defined by IPSS are variable and a subset of patients experience inferior than expected outcomes. Treatment with hypomethylating agents is the standard of care in higher-risk MDS, but there have been little data for hypomethylating therapy in LR MDS. We retrospectively collected and analyzed the data related to hypomethylating therapy in IPSS LR MDS from 12 Korean institutes.

Patients and Methods: A total of 610 patients, who were treated with azacitidine or decitabine for IPSS LR MDS, were included in this retrospective case series study. All patients received azacitidine (7-day) or decitabine (5-day). Both regimens were repeated every 4 weeks. The overall response rate (ORR) included rates for complete response (CR), partial response (PR), marrow CR (mCR), and stable disease (SD) with hematologic improvements (HI). For 139 patients who underwent allogeneic hematopoietic cell transplantation (HCT), all survival data were censored at the time of HCT.

Results: Median age was 63 (19-84) years. IPSS category was low in 44 and intermediate-1 in 566. The patients were reclassified with other scoring systems including revised IPSS (R-IPSS), WPSS, and LR-PSS, and between 21.8% and 37.7% of patients were identified as having high or very high risk features by the other prognostic indices. Patients received azacitidine (n=436) or decitabine (n=174) for a median of 5 (1-46) courses. ORR was 51.3% (CR 78, PR 12, mCR with HI 27, mCR without HI 20, and SD with HI 176). 294 patients (48.2%) showed any HI. Median OS was 2.35 years and patients with HI had significantly longer OS than those without HI (P=0.001). Our case series patients were well stratified in terms of OS by R-IPSS (P=0.001), WPSS (P<0.001), and LR-PSS (P<0.001).

Conclusion: IPSS LR MDS included a broad range of prognostic implications. Hypomethylating therapy brought varying degrees of response in about half of the patients with IPSS LR MDS. The patients who had high risk features with other prognostic indices showed poor OS and allogeneic HCT should be considered during the course of hypomethylating therapy in these patients.