Evaluation of Patients with Myelodysplastic Syndromes (MDS) Obtaining Stable Disease with the Use of Decitabine.

MDS is a group of hematologic malignancies associated with reduced quality of life related to progressive cytopenias and increased risk of infections and bleeding. Successful treatment in MDS is typically defined in terms of complete remission (CR). Treatment with decitabine, a DNA methyltransferase inhibitor, has led to CR in 9 to 39% of MDS patients. Many patients have responses that do not meet criteria for CR or partial remission, but may be of clinical importance, especially for older MDS patients. Since patients who achieve stable disease may receive benefits from treatment, it was of interest to evaluate patient characteristics and treatment response results of those who achieved stable disease with decitabine.

99 patients with de novo (n=88) or secondary (n=11) MDS were treated with decitabine, 20 mg/m² daily for 5 days every 4 weeks in an outpatient setting (Steensma et al. J Clin Oncol 2009). No dose reductions were allowed but dose delays were permissible. Any FAB, including CMML, were eligible if ECOG 0-2 and normal hepatic and renal function. Supportive care, including blood products, were permitted. G-CSF was permitted for serious infection or sepsis. Twenty-three patients (18 de novo and 5 secondary MDS) achieved stable disease as the best response by IWG 2006 criteria.

At baseline, stable disease patients had a median age of 75 years (70% >70 years) and were mainly men (70%). Ten patients had RA, 7 had RAEB, 4 had RAEB-t, and one each had RARS or CMML. The IPSS scores for these patients were Low (n = 1; 4%), INT-1 (n = 8; 35%), INT-2 (n = 5; 22%), and High (n = 9; 39%). Cytogenetics were good 10 (43%), 1 (4%) intermediate, 10 (43%) poor, or unknown 2 (9%). At baseline 19 (83%) were RBC transfusion dependent, 3 (13%) platelet transfusion dependent. 22 patients were ECOG 0-1. Five patients had received prior cytotoxic chemotherapy, none with azacitidine or decitabine. The median number of cycles initiated was 5.0 (range 2 – 19). At the time of the analysis, 12 of the 23 patients had died with a median survival of 19.2 months (95% CI: 9.4, not estimable). This is consistent with the survival response (19.4 months (95% CI: 15, not estimable) for the entire cohort, which included the stable disease patients, 50% who achieved a hematologic improvement or better, and 10% with progressive disease with decitabine (15% not assessable). Median time to AML or death was 16.1 months (95% CI: 7.2, not estimable). Three of 19 RBC-dependent patients at baseline became transfusion independent for at least 8 weeks with treatment. Conversely, 3 of 4 baseline RBC-independent patients became transfusion dependent. One of 3 platelet-dependent patients became transfusion independent. Three of 20 platelet-independent patients at baseline became transfusion dependent. Of ten patients evaluable for cytogenetic responses, 2 patients had partial cytogenetic responses. Eleven out of 23 patients had at least one related SAE. Myelosuppression-related adverse events were common (≥10%) in these 23 patients with grade 3 or higher adverse experiences of anemia (26%), febrile neutropenia (17%), neutropenia (39%), and thrombocytopenia (30%).

In an outpatient setting, approximately one-quarter of MDS patients maintained stable disease with decitabine treatment, with acceptable and manageable toxicity. Overall survival in this subset of patients appeared to be similar to that observed with the entire cohort, which included 50% of patients with an objective clinical benefit. Larger analyses are needed to fully understand the characteristics of and treatment-related benefits for patients who achieve stable disease with decitabine treatment.

No relevant conflicts of interest to declare.