Decitabine Induces Responses in Patients with Myelodysplastic Syndrome (MDS) after Failure of Azacitidine Therapy.

Background

The hypomethylating agents azacitidine and decitabine are active in MDS and approved in the U.S.A. for this indication. The comparative efficacy of these two agents is not established. Responses to one drug after treatment failure with the other may offer evidence for superior efficacy.

Study Aims

Evaluate the efficacy of decitabine in MDS after failure of azacitidine therapy.

Study Group and Treatment

Adults with MDS who have progressed or failed to respond after at least three courses of azacitidine were eligible. Other entry criteria were standard including performance status 0–2, normal liver, kidney, and cardiac functions, and informed consent. Patients received decitabine 20 mg/m² IV/D x 5 every four weeks. Response was evaluated by the modified IWG criteria (Cheson, Blood 2006).

Results

Fourteen patients have been treated to date. Their median age was 74 years (range 58–85 years). Patients had received prior azacitidine for a median of 4 courses (range 1 to 9); number of azacitidine courses 3 or more in 12 patients (86%); hemoglobin less than 10 g/dL in 7 (50%); thrombocytopenia < 100 x 10⁹/L in 11 (78%); chromosomal abnormalities in 6 (43%); marrow or peripheral blast 5% or more in 13 (93%). Overall, 5 patients (36%) achieved IWG response: CR in 3 (21%), PR in 1 (7%), marrow CR +/− other hematologic improvements (HI) in 1 (7%). Improvement of thrombocytopenia was noted in 2/5 patients (40%) with pretreatment platelets < 50 x 10⁹/L. Median remission duration was 5.3 months; median survival was 6.0 months. Extramedullary toxicities were minimal.

Conclusions

Decitabine is active in MDS following failure of azacitidine therapy. Comparative randomized studies of decitabine versus azacitidine in MDS may be indicated.