Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents

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

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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.

Original languageEnglish (US)
Pages (from-to)599-606
Number of pages8
JournalAmerican Journal of Hematology
Volume92
Issue number7
DOIs
StatePublished - Jul 2017
Externally publishedYes

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ASJC Scopus subject areas

  • Hematology

Cite this

Alfonso, A., Montalban-Bravo, G., Takahashi, K., Jabbour, E. J., Kadia, T., Ravandi, F., Cortes, J., Estrov, Z., Borthakur, G., Pemmaraju, N., Konopleva, M., Bueso-Ramos, C., Pierce, S., Kantarjian, H., & Garcia-Manero, G. (2017). Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents. American Journal of Hematology, 92(7), 599-606. https://doi.org/10.1002/ajh.24735