Decitabine Induces High Response Rates in Patients with Chronic Myelomonocytic Leukemia (CMML).

Background The hypomethylating agents decitabine and azacitidine have significant anti-myelodysplastic (MDS)activity and have been FDA approved for the treatment of MDS and CMML. Experience in CMML has been minimal.

Study Aims Evaluate the efficacy of decitabine in CMML.

Study Group and Treatment Patients with CMML received decitabine 20 mg/m² IV/1 hour daily x 5 or 2 alternative schedules, delivering 100 mg/m²/course every four weeks (Kantarjian, Blood 2006). Response was evaluated by the modified IWG criteria (Cheson, Blood 2006).

Results Nineteen patients were treated. Their median age was 66 years (range 44–82 years). Splenomegaly was present in 4 (21%); hemoglobin less than 10 g/dL in 10 (53%); thrombocytopenia less than 100 x 10⁹/L in 12 (63%); WBC more than 40 x 10⁹/L in 5 (26%); chromosomal abnormalities in 6 (32%); prior therapy for CMML in 9 (47%); marrow or peripheral blast 5% or more in 11 (58%). Overall, 13 patients (69%) achieved IWG responses: CR in 11 (58%), other HI in 2 (11%). Improvement of thrombocytopenia was noted in 7/8 patients (88%) with pretreatment platelets less than 50 x 10⁹/L. Median survival was 19 months. Among 6 patients with pretreatment chromosomal abnormalities who achieved response, 1 (17%) had disappearance, and 2 had > 50% reduction of cytogenetic abnormalities. Extramedullary toxicities were minimal.

Conclusions Decitabine is active and safe in CMML. Future studies may combine decitabine with histone deacetylase inhibitors, chemotherapy (eg cytarabine, topotecan), or growth factors.