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. 2017 Jul;92(7):599-606.
doi: 10.1002/ajh.24735. Epub 2017 May 26.

Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents

Ana Alfonso  1 , Guillermo Montalban-Bravo  1 , Koichi Takahashi  1 , Elias J Jabbour  1 , Tapan Kadia  1 , Farhad Ravandi  1 , Jorge Cortes  1 , Zeev Estrov  1 , Gautam Borthakur  1 , Naveen Pemmaraju  1 , Marina Konopleva  1 , Carlos Bueso-Ramos  2 , Sherry Pierce  1 , Hagop Kantarjian  1 , Guillermo Garcia-Manero  1
Affiliations

Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents

Ana Alfonso et al. Am J Hematol. 2017 Jul.

Abstract

Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML-specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n = 151) treated with HMA. Mean age at diagnosis was 69 years (range 50-88). According to the CMML-specific prognostic scoring system (CPSS): 17 (15%) were low-risk, 45 (39%) intermediate-1 risk, 42 (36%) intermediate-2, and 12 (10%) high-risk. 35 (23%) patients received single agent azacitidine, 73 (48%) single agent decitabine, and 43 (29%) combinations. With a median follow-up of 17 months, overall response rate (ORR) was 75%, with 41% achieving complete response (CR). Median overall survival (OS) was 24 months (95%CI: 20-28) and event-free survival 14 months (95%CI: 11-17). By multivariate analysis, age < 70 years, higher levels of hemoglobin, absence of blast in peripheral blood and lower CPSS cytogenetic risk predicted for better OS. CR was significantly higher in those patients treated with decitabine (58.3%) when compared with azacitidine (20.6%) (P < .001). 13 patients (9%) received allo-SCT after a median of 4 cycles of HMA. 66 patients (50%) had HMA failure: 26 primary (34%) and 50 secondary (66%), including 35 (46%) that transformed to AML. Outcomes after HMA failure were poor with OS of 7 months (95%CI: 3-12). In conclusion, HMA are effective in CMML but new agents and combinations are needed. This data could be a benchmark for further drug development in CMML.

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Figures

Figure 1
Figure 1. Flow chart of CMML patients receiving hypomethylating agents
CMML: chronic myelomonocytic leukemia; allo-SCT: allogeneic stem cell transplant; HDAC: histone deacetylase.
Figure 2
Figure 2. Overall survival (OS), leukemia-free survival (LFS) and event-free survival (EFS) for patients with CMML treated with hypomethylating agents
(A) OS, (B) LFS and (C) EFS of the 151 CMML patients treated with hypomethylating agents.
See this image and copyright information in PMC

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