Abstract
Abstract 2936
Decitabine is a hypomethylating agent (HMA) with demonstrated activity and an acceptable safety profile for the treatment of all FAB subtypes of myelodysplastic syndromes (MDS). A retrospective analysis was conducted to determine the effect of prior MDS treatment on overall response rate (ORR), duration of response, time to response, and overall survival (OS).
Of 188 patients, 54 had prior MDS treatment consisting of cytotoxic chemotherapy (n=31), immunomodulators (n=21), stem cell transplant (n=4), monoclonal antibodies (n=2), oblimersen (n=1), or HMAs (n=1) were identified from two clinical trials with decitabine (Phase III, 3-day and Phase II, 5-day dosing studies). Patients were stratified on the basis of those who had received prior treatment (PT, n=54) for MDS and those who had not (NPT, n=134). Descriptive statistics were used to quantify the differences between the two groups for baseline characteristics, response rates (based on IWG 2006 criteria), safety and survival data.
Baseline characteristics showed the PT group had a longer time from diagnosis; the NPT group had a greater percentage of patients with High risk and Int-2 IPSS scores. There were differences noted in the baseline NPT group (5-day dosing only), with more patients with FAB classification of RAEB and RAEB-t (n=45), whereas the baseline PT group had a greater number of CMML patients (n=8). Objective response rate (ORR), overall improvement rate (OIR) and median survival were greater in NPT patients with no significant difference observed between the groups (Table 1). Patients with PT had a shorter duration of improvement (median 208 days) vs. the NPT group (median 296 days, p=NS) for the 5-day dosing study.
Decitabine is active in patients with MDS with low rate of side effects. Prior therapy with intensive regimens have no impact on response to decitabine and such patients should be considered for hypomethylating therapy.
| DACO-007 Study (N=89) | DACO-020 Study (N=99) | |||||
|---|---|---|---|---|---|---|
| PT (n=27) | NPT(n=72) | Chi Square | PT(n=) | NPT(n=) | Chi Square | |
| ORR, % (CR+PR) | 11.1(n=3) | 19.3(n=12) | NS | 25.9(n=7) | 36.1(n=26) | NS |
| ORI, % (CR+PR+HI) | 22.2(n=6) | 32.3(n=20) | NS | 44.4(n=12) | 54.2(n=39) | NS |
| Median OS, days (95% CI) | 334(183–583) | 462(319–513) | NS | 548(184–802) | 582(447–760) | NS |
| DACO-007 Study (N=89) | DACO-020 Study (N=99) | |||||
|---|---|---|---|---|---|---|
| PT (n=27) | NPT(n=72) | Chi Square | PT(n=) | NPT(n=) | Chi Square | |
| ORR, % (CR+PR) | 11.1(n=3) | 19.3(n=12) | NS | 25.9(n=7) | 36.1(n=26) | NS |
| ORI, % (CR+PR+HI) | 22.2(n=6) | 32.3(n=20) | NS | 44.4(n=12) | 54.2(n=39) | NS |
| Median OS, days (95% CI) | 334(183–583) | 462(319–513) | NS | 548(184–802) | 582(447–760) | NS |
Jabbour:Eisai Inc.: Editorial and statistical support, Honoraria. Kantarjian:Novartis: Research Funding; Pfizer: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Consultancy. Borthakur:Eisai Inc.: Research Funding. Cortes:Novartis: Research Funding; Pfizer: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding. Ravandi:Eisai Inc.: Research Funding; Eisai Inc.: Honoraria.
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