A retrospective analysis of upfront treatment strategies in chronic myelomonocytic leukemia: impact on survival and response patterns.

In a retrospective analysis of 457 Mayo Clinic patients (median age 72 years) with chronic myelomonocytic leukemia (CMML) (proliferative 38%; CMML-2 15%), overall survival (OS), calculated from time of diagnosis, was not differentially affected by treatment exposure to: i) either cytotoxic or non-cytotoxic drugs (i.e., untreated; N=155; median 29 months); ii) non-cytotoxic drugs (N=95; median 25 months); iii) hydroxyurea (HU; N=102; median 23 months) or hypomethylating agent (HMA; N=78; median 35 months), as the first-line choice of cytotoxic therapy; or iv) cytotoxic drugs other than HU or HMA (N=27; median 18 months) (P=0.2). Blast transformation (BT) was more frequent in patients exposed to cytotoxic (26%) versus non-cytotoxic (11%) drugs (P<0.01), confirmed in multivariable analysis (HR [Hazard Ratio] 2.0; 95% Confidence Interval [CI]: 1.2-3.3) that accounted for other risk factors. Comparison of patients receiving HU or HMA favored HMA for control of leukocytosis (P<0.01), anemia (P=0.02), and thrombocytopenia (P=0.06); however, there was no difference in OS (P=0.3) or BTfree survival (P=0.7) between the two treatment arms. RUNX1 mutation was associated with lower response rates in leukocytosis (P=0.03) and thrombocytopenia (P=0.03) in HU/HMA treated patients. Allogeneic stem cell transplantation was undertaken in 49 patients with median post-transplant survival of 69 months. Our study confirms that current drug therapy in CMML has no impact on OS. Instead, it suggests a significant association between BT and the need for cytotoxic drug therapy. Our observations regarding higher response rates with HMA versus HU are also in line with a previously published controlled study.