TY - JOUR
T1 - Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients
AU - Coston, Tucker
AU - Pophali, Prateek
AU - Vallapureddy, Rangit
AU - Lasho, Terra L.
AU - Finke, Christy M.
AU - Ketterling, Rhett P.
AU - Carr, Ryan
AU - Binder, Moritz
AU - Mangaonkar, Abhishek A.
AU - Gangat, Naseema
AU - Al-Kali, Aref
AU - Litzow, Mark
AU - Zblewski, Darci
AU - Pardanani, Animesh
AU - Tefferi, Ayalew
AU - Patnaik, Mrinal M.
N1 - Funding Information:
information National Center for Advancing Translational Sciences, Grant/Award Number: KL2 TR000136 Current publication is supported in part by grants from the “The Gerstner Family Career Development Award” and the Mayo Clinic Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.” This publication was supported by CTSA Grant Number KL2 TR000136 from the National Center for Advancing Translational Science (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Funding Information:
Current publication is supported in part by grants from the “The Gerstner Family Career Development Award” and the Mayo Clinic Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.” This publication was supported by CTSA Grant Number KL2 TR000136 from the National Center for Advancing Translational Science (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/7
Y1 - 2019/7
N2 - Hypomethylating agents (HMA) are currently the only FDA approved therapy for patients with chronic myelomonocytic leukemia (CMML). In the current retrospective study, we assessed response rates as adjudicated by the IWG (International Working Group) MDS (myelodysplastic syndrome) and MDS/MPN myeloproliferative neoplasm overlap syndrome response criteria, in 121 CMML patients treated with Azacitidine (AZA, n = 56) and Decitabine (DAC, n = 65). The overall response rates were 41% by the IWG MDS (AZA- 45%, DAC-39%), and 56% by the IWG MDS/MPN (AZA-56%, DAC-58%) response criteria, with CR (complete remission) rates of <20% for both agents, by both criteria. There were no significant differences in response rates between proliferative and dysplastic CMML. Moreover, 29% of CMML patients in a CR with HMA progressed to AML (blast transformation), underscoring the limited impact of these agents on disease biology. Progression after HMA response was associated with a median overall-survival (OS) of 8 months, while median OS in patients with primary HMA failure was 4 months. Lower serum LDH levels (<250 Units/L) were associated with HMA responses by both criteria; while ASXL1 and TET2 mutational status had no impact. HMA treated patients had a longer median OS (31 vs 18 months; P =.01), in comparison to those treated with conventional care regimens (excluding observation only patients), without any differences between AZA vs DAC (P =.37). In conclusion, 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.
AB - Hypomethylating agents (HMA) are currently the only FDA approved therapy for patients with chronic myelomonocytic leukemia (CMML). In the current retrospective study, we assessed response rates as adjudicated by the IWG (International Working Group) MDS (myelodysplastic syndrome) and MDS/MPN myeloproliferative neoplasm overlap syndrome response criteria, in 121 CMML patients treated with Azacitidine (AZA, n = 56) and Decitabine (DAC, n = 65). The overall response rates were 41% by the IWG MDS (AZA- 45%, DAC-39%), and 56% by the IWG MDS/MPN (AZA-56%, DAC-58%) response criteria, with CR (complete remission) rates of <20% for both agents, by both criteria. There were no significant differences in response rates between proliferative and dysplastic CMML. Moreover, 29% of CMML patients in a CR with HMA progressed to AML (blast transformation), underscoring the limited impact of these agents on disease biology. Progression after HMA response was associated with a median overall-survival (OS) of 8 months, while median OS in patients with primary HMA failure was 4 months. Lower serum LDH levels (<250 Units/L) were associated with HMA responses by both criteria; while ASXL1 and TET2 mutational status had no impact. HMA treated patients had a longer median OS (31 vs 18 months; P =.01), in comparison to those treated with conventional care regimens (excluding observation only patients), without any differences between AZA vs DAC (P =.37). In conclusion, 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.
UR - http://www.scopus.com/inward/record.url?scp=85065222679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065222679&partnerID=8YFLogxK
U2 - 10.1002/ajh.25488
DO - 10.1002/ajh.25488
M3 - Article
C2 - 30964202
AN - SCOPUS:85065222679
SN - 0361-8609
VL - 94
SP - 767
EP - 779
JO - American journal of hematology
JF - American journal of hematology
IS - 7
ER -