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

Abstract

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) neither cytotoxic nor non-cytotoxic drugs (i.e., untreated; N=155; median 29 months), ii) non-cytotoxic drugs (N=95; 25 months), iii) hydroxyurea (HU; N=102; 23 months) or hypomethylating agent (HMA; N=78; 35 months), as the first-line choice of cytotoxic therapy, or iv) cytotoxic drugs other than HU or HMA (N=27; 18 months) [p=0.2]. Blast transformation (BT) was more frequent in patients exposed to cytotoxic (26%) vs. non-cytotoxic (11%) drugs (p<0.01), confirmed in multivariable analysis (HR 2.0; 95% 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 BT-free 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 the lack of OS impact from current drug therapy in CMML and instead suggests a significant association between BT and the need for cytotoxic drug therapy. Our observations regarding higher response rates with HMA vs. HU are also in line with a previously published controlled study.