Survival and Efficacy of Decitabine in Myelodysplastic Syndromes (MDS), Analysis of the 5-Day IV Dosing Regimen.

Abstract

An optimized dosing regimen for decitabine, an epigenetic therapy approved for the treatment of MDS, has been described recently based on the results of a single center, Phase II three arm adaptive randomization study (Kantarjian et al, Cancer 2007; 109:265–273). The results of this trial have been described in the context of a pooled data set from all three treatment arms; only a limited set of data specific to the 5-day IV dosing arm has been presented. Here, we provide an in-depth update of important efficacy and toxicity endpoints specific to the 93 patients treated within this trial with the 5-day schedule. 39/93 patients were not categorized (N/C) by IPSS due to exclusion from IPSS (extensive prior therapy, secondary MDS). Distribution by IPSS in the 54 categorized patients was: Intermediate-1 (INT-1) 26%, Intermediate-2 (INT-2) 50%, and High risk (HR) 24%. The median age was 65 years (range 37–83). Abnormal chromosomes were observed in 62%, 47% had >10% bone marrow blasts; 96% had various degrees of cytopenias. Secondary MDS was documented in 28 patients (30%). The median duration of MDS was 2.5 months. Prior therapy for MDS was given to 52 pts (56%): growth factors only in 34; chemotherapy ± growth factors 18. Overall 36 pts (39%) pts achieved CR, and 75 (81%) had a response by IWG criteria. The response rates by IWG criteria with IPSS subsets were: INT-1 71% (9 CR, 1 marrow CR); INT-2 70% (9 CR, 6 hematologic improvement [HI], 4 marrow CR); HR 62% (4 CR, 3 HI, 1 marrow CR); and N/C 72% (14 CR, 1 PR, 6 HI, 7 marrow CR). The median number of cycles was 8+. The median time to response was 2.3 months. The median duration of CR was 14 months (range 3 to 16+ months). The median time to acute myeloid leukemia (AML) transformation or death was 15 months. The median time to AML (censoring for death without AML) was 30 months. The median survival was 20 months, with 1- and 2-year survival rates of 61% and 41%, respectively. The side effect profile for the 5-day IV regimen was consistent with what has been previously reported, with Grade 3–4 drug-related extramedullary side effects being uncommon. The encouraging survival and response rates of the 5-day dosing regimen of decitabine in this poor-prognosis population, coupled with its manageable side effect profile, provide a beneficial therapeutic option and a foundation for further advances for patients with MDS.