Decitabine has shown clinical benefits in patients with International Prognostic Scoring System (IPSS) intermediate (INT)-2 or high risk myelodysplastic syndrome (MDS), but the benefits have not been well defined in patients with lower-risk disease group (IPSS low or INT-1). Recently, it was proposed that the prognosis for patients with lower-risk disease is heterogeneous, with a substantial fraction of these patients having poor survival. Therefore, we classified IPSS lower-risk MDS patients using the Lower-Risk Prognostic Scoring System (LR-PSS) and then identified clinical outcomes after decitabine treatment in each subgroup.
Two observational studies (DIVA [NCT01041846] and DRAMA [NCT01400633]) on the effectiveness of decitabine treatment in patients with IPSS INT-1, 2, or high risk MDS were previously conducted. This analysis included patients with IPSS INT-1 risk disease from these two studies, and the patients were classified into one of the LR-PSS categories (category 1, 2, or 3) classifying patients by clinical variables such as cytogenetic, age, hemoglobin, platelet levels, and bone marrow blast percentage, so that patients with higher scores would be classified into higher risk categories. Patients in each LR-PSS category were divided by response or non-response to decitabine treatment. Overall response rate (ORR) included complete response (CR), partial response, marrow CR with or without hematologic improvement (HI), and stable disease with HI by the modified IWG 2006 response criteria. The overall survival (OS) in each subgroup was calculated and we analyzed differences in survival by response in each category group.
A total of 130 patients were included in this analysis: 12 patients (9.2%) in LR-PSS category 1, 65 (50.0%) in category 2, and 53 (40.8%) in category 3. Patients in LR-PSS category 3 were older, predominantly male, and had more comorbidities. Overall refractory cytopenia with multilineage dysplasia (RCMD) was the most common WHO subtype (53/130, 40.8%), but there was a trend toward more patients with refractory anemia with excess of blasts (RAEB-1) in LR-PSS category 3. Transfusion dependency at baseline was more common in LR-PSS category 3. ORR was observed in 74 patients (56.9%) after decitabine treatment: there was no significant difference in ORR between the LR-PSS groups (category 1, 58.3%; category 2, 56.9%; and category 3, 56.6%, P = 0.9940). Unlike patients in category 1 or 2, those in category 3 showed a significant difference in OS between responders and non-responders (P = 0.0015). A higher platelet count at baseline (≥50 x 109/L) was a favorable predictor of ORR (odds ratio, 2.24; 95% confidence interval [CI], 1.03 to 4.84) and a patient with lower percentage of bone marrow blasts at baseline (<4%) showed significantly lower ORR (odds ratio, 0.26; 95% CI, 0.12 to 0.56). The presence of comorbidities was the only variable significantly associated with OS in Cox proportional hazards regression model (hazard ratio, 0.35; 95% CI, 0.129 to 0.922).
Decitabine treatment was effective in patients with lower-risk disease and showed a survival benefit in patients with lower-risk MDS classified as LR-PSS category 3 who responded to treatment.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.