Clinical Experience of Decitabine in Elderly Patients with Myelodysplastic Syndromes (MDS).

Decitabine, a potent DNA hypomethylating agent, has demonstrated efficacy in MDS patients. The incidence of MDS increases with age, with limited treatment options for these patients. With advancing age, patients are generally less tolerant of treatment and suffer from more comorbidities. Important goals of therapy are to improve transfusion dependence and to delay progression of disease, with favorable toxicity. This subgroup analysis evaluated the effect of decitabine on overall response rate (ORR), duration of response, time to response, transfusion independence, and tolerability in subgroups of older patients (65-75 and >75 years of age).

Data used in these analyses were from two previously published clinical trials (Steensma et al. J Clin Oncol, 2009 [DACO-020] and Kantarjian et al. Cancer 2006 [DACO-007]). In both trials, eligible patients were ≥18 years of age and had MDS (de novo or secondary) of any French-American-British subtype and an International Prognostic Scoring System score ≥0.5. In DACO-020, patients were treated with decitabine 20 mg/m² IV daily for 5 consecutive days every 4 weeks. Response rate was assessed with the International Working Group (IWG 2006) criteria in DACO-020. In DACO-007, patients were treated with decitabine 15 mg/m² IV over 3 hours every 8 hours for 3 consecutive days every 6 weeks. Response rate was assessed with the IWG 2000 criteria in DACO-007.

In DACO-020, baseline disease characteristics were generally similar between groups, except more patients in the 65-75 age group (n = 58) had RARS (19% vs. 4%) or RAEB (50% vs. 38%) and fewer had RA (12% vs. 38%) compared to patients in the >75 age group (n = 26). Further, more patients in the >75 group were transfusion dependent at baseline (77% vs. 57%).

Grade 3-4 anemia, leukopenia, neutropenia, and thrombocytopenia were less frequent (22, 5, 35, and 22%, respectively) in patients in the 65-75 age group versus patients in the >75 age group (27, 8, 46, and 35%, respectively). Remarkably, however, there were no reports of febrile neutropenia in >75 age group (26% in the 65-75 age group).

In this subgroup analysis, decitabine is an effective and generally well tolerated treatment strategy, even in elderly patients with MDS. Despite the advanced age, responses were more rapid and more durable in the mature elderly than younger patients. The slightly higher hematological toxicity did not translate into increased infectious risk, with no febrile neutropenic episodes in patients over age 75 in these studies. These data suggest that the goals of therapy do not need to be stratified by age, and support future trials of decitabine in elderly and other at-risk populations with MDS.

Geils:Eisai Inc. : Speakers Bureau.