Bazinet Alexandre, Darbaniyan Faezeh, Kadia Tapan M, Venugopal Sangeetha, Kanagal-Shamanna Rashmi, DiNardo Courtney D, Borthakur Gautam, Jabbour Elias J, Daver Naval G, Pemmaraju Naveen, Konopleva Marina Y, Ravandi Farhad, Sasaki Koji, Chien Kelly S, Hammond Danielle, Pierce Sherry A, Kantarjian Hagop M, Garcia-Manero Guillermo, Montalban-Bravo Guillermo
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cancer. 2023 Feb 15;129(4):560-568. doi: 10.1002/cncr.34564. Epub 2022 Dec 2.
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).
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.
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.
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.
除羟基脲和低甲基化药物（HMA）外，高危慢性粒单核细胞白血病（CMML）患者的治疗选择有限。基于克拉屈滨（CLAD）、小剂量阿糖胞苷（LDAC）和HMA的方案是治疗急性髓系白血病（AML）的有效低强度疗法。
作者进行了一项回顾性病历审查，以评估CLAD/LDAC/HMA方案对CMML以及由CMML引起的继发性急性髓系白血病（sAML）的疗效。根据2006年国际工作组CMML标准和2017年欧洲白血病网AML标准评估反应。采用Kaplan-Meier法评估总生存期（OS）、无白血病生存期（LFS）和缓解持续时间。根据既往HMA暴露情况对患者进行分层。
作者确定了21例接受基于CLAD/LDAC/HMA方案治疗的CMML患者（8例未接受过HMA治疗的CMML患者和13例HMA治疗失败的CMML患者）以及33例sAML患者（11例未接受过HMA治疗的sAML患者和22例HMA治疗失败的sAML患者）。CMML队列中高危特征（增殖型、原始细胞升高和RAS/MAPK突变）更为常见。CMML的总缓解率为33%（未接受过HMA治疗的CMML患者为50%，HMA治疗失败的CMML患者为23%），sAML为48%（未接受过HMA治疗的sAML患者为82%，HMA治疗失败的sAML患者为32%）。未接受过HMA治疗的CMML、HMA治疗失败的CMML、未接受过HMA治疗的sAML和HMA治疗失败的sAML的中位OS分别为14.4个月、8.8个月、42.9个月和2.9个月。未接受过HMA治疗的CMML和HMA治疗失败的CMML的中位LFS分别为14.4个月和3.9个月。
基于CLAD/LDAC/HMA的方案对部分高危CMML患者以及由CMML引起的sAML患者有效，这些患者此前未经历过HMA治疗失败。这些发现必须在前瞻性研究中得到证实。
