TY - JOUR
T1 - A retrospective study of cladribine and low-dose cytarabine–based regimens for the treatment of chronic myelomonocytic leukemia and secondary acute myeloid leukemia
AU - Bazinet, Alexandre
AU - Darbaniyan, Faezeh
AU - Kadia, Tapan M.
AU - Venugopal, Sangeetha
AU - Kanagal-Shamanna, Rashmi
AU - DiNardo, Courtney D.
AU - Borthakur, Gautam
AU - Jabbour, Elias J.
AU - Daver, Naval G.
AU - Pemmaraju, Naveen
AU - Konopleva, Marina Y.
AU - Ravandi, Farhad
AU - Sasaki, Koji
AU - Chien, Kelly S.
AU - Hammond, Danielle
AU - Pierce, Sherry A.
AU - Kantarjian, Hagop M.
AU - Garcia-Manero, Guillermo
AU - Montalban-Bravo, Guillermo
N1 - Publisher Copyright:
© 2022 American Cancer Society.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - Background: Patients with higher risk chronic myelomonocytic leukemia (CMML) have limited therapeutic options beyond hydroxyurea and hypomethylating agents (HMAs). Regimens based on a backbone of cladribine (CLAD), low-dose cytarabine (LDAC), and an HMA are effective low-intensity therapies for acute myeloid leukemia (AML). Methods: The authors conducted a retrospective chart review to evaluate the efficacy of CLAD/LDAC/HMA in CMML and secondary acute myeloid leukemia (sAML) arising from CMML. Responses were evaluated according to the 2006 International Working Group criteria for CMML and the 2017 European LeukemiaNet criteria for AML. The overall survival (OS), leukemia-free survival (LFS), and duration of response were evaluated with the Kaplan–Meier method. Patients were stratified on the basis of prior HMA exposure. Results: The authors identified 21 patients with CMML (eight with HMA-naive CMML and 13 with HMA-failure CMML) and 33 patients with sAML (11 with HMA-naive sAML and 22 with HMA-failure sAML) treated with CLAD/LDAC/HMA-based regimens. The CMML cohort was enriched for high-risk features (proliferative type, elevated blasts, and RAS/MAPK mutations). The overall response rate was 33% in CMML (50% in HMA-naive CMML and 23% in HMA-failure CMML) and 48% in sAML (82% in HMA-naive sAML and 32% in HMA-failure sAML). The median OS was 14.4, 8.8, 42.9, and 2.9 months for HMA-naive CMML, HMA-failure CMML, HMA-naive sAML, and HMA-failure sAML, respectively. The median LFS was 14.4 and 3.9 months for HMA-naive CMML and HMA-failure CMML, respectively. Conclusions: CLAD/LDAC/HMA-based regimens are effective in a subset of patients with higher risk CMML and sAML arising from CMML who have not previously experienced HMA failure. These findings must be confirmed in prospective studies.
AB - Background: Patients with higher risk chronic myelomonocytic leukemia (CMML) have limited therapeutic options beyond hydroxyurea and hypomethylating agents (HMAs). Regimens based on a backbone of cladribine (CLAD), low-dose cytarabine (LDAC), and an HMA are effective low-intensity therapies for acute myeloid leukemia (AML). Methods: The authors conducted a retrospective chart review to evaluate the efficacy of CLAD/LDAC/HMA in CMML and secondary acute myeloid leukemia (sAML) arising from CMML. Responses were evaluated according to the 2006 International Working Group criteria for CMML and the 2017 European LeukemiaNet criteria for AML. The overall survival (OS), leukemia-free survival (LFS), and duration of response were evaluated with the Kaplan–Meier method. Patients were stratified on the basis of prior HMA exposure. Results: The authors identified 21 patients with CMML (eight with HMA-naive CMML and 13 with HMA-failure CMML) and 33 patients with sAML (11 with HMA-naive sAML and 22 with HMA-failure sAML) treated with CLAD/LDAC/HMA-based regimens. The CMML cohort was enriched for high-risk features (proliferative type, elevated blasts, and RAS/MAPK mutations). The overall response rate was 33% in CMML (50% in HMA-naive CMML and 23% in HMA-failure CMML) and 48% in sAML (82% in HMA-naive sAML and 32% in HMA-failure sAML). The median OS was 14.4, 8.8, 42.9, and 2.9 months for HMA-naive CMML, HMA-failure CMML, HMA-naive sAML, and HMA-failure sAML, respectively. The median LFS was 14.4 and 3.9 months for HMA-naive CMML and HMA-failure CMML, respectively. Conclusions: CLAD/LDAC/HMA-based regimens are effective in a subset of patients with higher risk CMML and sAML arising from CMML who have not previously experienced HMA failure. These findings must be confirmed in prospective studies.
KW - acute myeloid leukemia
KW - chronic myelomonocytic leukemia
KW - cladribine
KW - cytarabine
KW - hypomethylating agents
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U2 - 10.1002/cncr.34564
DO - 10.1002/cncr.34564
M3 - Article
C2 - 36458426
AN - SCOPUS:85143722334
SN - 0008-543X
VL - 129
SP - 560
EP - 568
JO - Cancer
JF - Cancer
IS - 4
ER -