Despite being the only therapy approved by the US Food and Drug Administration for patients with chronic myelomonocytic leukemia (CMML), hypomethylating agents (HMAs) appear to yield suboptimal response rates when assessed with either older or newer response criteria, according to a study published in the American Journal of Hematology.

Researchers at the Mayo Clinic retrospectively assessed response rates of 121 patients with CMML, as defined by the 2006 International Working Group (IWG) myelodysplastic syndrome (MDS) criteria or the 2015 MDS/myeloproliferative neoplasm (MPN) overlap syndrome criteria, being treated with azacitidine (56 patients) or decitabine (65 patients). The team also checked for associations between predictors of response to HMAs, including gene mutations, and survival.

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The median age was 68 years (range, 18-85). For the IWG MDS criteria, the overall response rate was 41% (azacitidine, 45%; decitabine, 39%). For the IWG MDS/MPN criteria, the overall response rate was 56% (azacitidine, 56%; decitabine, 58%). For both sets of criteria, and for both HMAs, complete remission (CR) rates were below 20%. No differences in response rates were identified between proliferative and dysplastic CMML.

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Of patients in CR with an HMA, 29% progressed to acute myeloid leukemia (AML). Median overall survival (OS) was 4 months in patients with primary HMA failure and 8 months after progression following HMA response.

Of the predictors of response to HMA, serum lactate dehydrogenase (< 250 units/L) was associated with HMA responses according to both criteria. However, the mutational status of ASXL1 and TET2 was not significant (P =.79 and P =.45, respectively).

HMA-treated patients had longer median OS (31 vs 18 months; P =.01) compared with patients treated with conventional care regimens. No differences were seen between patients treated with azacitidine or decitabine (P =.37).

The authors concluded that “this study highlights the inadequacies of HMA therapy in CMML, retrospectively validates the IWG MDS/MPN response criteria, and underscores the need for newer, rationally derived therapies.”


Coston T, Pophali P, Vallapureddy R, et al. Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients [published online April 9, 2019]. Am J Hematol. doi:10.1002/ajh.25488

This article originally appeared on Hematology Advisor