TY - JOUR
T1 - Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents
AU - Alfonso, Ana
AU - Montalban-Bravo, Guillermo
AU - Takahashi, Koichi
AU - Jabbour, Elias J.
AU - Kadia, Tapan
AU - Ravandi, Farhad
AU - Cortes, Jorge
AU - Estrov, Zeev
AU - Borthakur, Gautam
AU - Pemmaraju, Naveen
AU - Konopleva, Marina
AU - Bueso-Ramos, Carlos
AU - Pierce, Sherry
AU - Kantarjian, Hagop
AU - Garcia-Manero, Guillermo
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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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U2 - 10.1002/ajh.24735
DO - 10.1002/ajh.24735
M3 - Article
C2 - 28370097
AN - SCOPUS:85019314016
SN - 0361-8609
VL - 92
SP - 599
EP - 606
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 7
ER -