Treatment of Chronic Myelomonocytic Leukemia: Decitabine vs. Hydroxyurea

The myeloproliferative subtype of chronic myelomonocytic leukemia (MP-CMML) has a poor prognosis among patients who are ineligible for allogeneic hematopoietic cell transplantation. Hydroxyurea and the hypomethylating agent decitabine have clinical activity in controlling elevated white blood counts (WBC) and reducing myeloblasts. Investigators compared these agents as initial therapy for CMML in a multinational, industry-sponsored, phase 3 trial.

One hundred seventy patients were randomized to oral hydroxyurea, titrated from 1 to 4 g daily to maintain WBC within the normal range, or to intravenous decitabine, given at 20 mg/m² on days 1 to 5 of each 28-day cycle. Erythroid- and platelet-stimulating agents were not allowed. Treatment continued until disease progression, leukemic transformation, unacceptable toxicity, or death.

After completing three cycles of therapy, 56% of patients in the decitabine arm achieved response compared with 31% in the hydroxyurea arm (P=.002); rates of complete remission and marrow remission with hematologic improvement were also higher with decitabine. However, at a median 17.5 months' follow-up, median event-free survival (EFS; the primary endpoint) and overall survival (OS) did not differ significantly between groups (EFS: 12.1 months with decitabine and 10.3 months with hydroxyurea; OS: 18.4 and 21.9 months, respectively). The decitabine arm had a higher incidence of adverse events, including infections, hospitalizations, and cardiovascular events, as well as mortality (14 deaths with decitabine vs. 9 with hydroxyurea while on treatment).