Ye Li, Mei Chen, Ren Yanling, Zhou Xinping, Ma Liya, Xu Weilai, Wei Juying, Jiang Huifang, Zhang Liming, Zeng Hui, Tong Hongyan
MDS Center, Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
Key Laboratory of Hematologic Malignancies of Zhejiang Province, Hangzhou 310009, Zhejiang Province, China.
J Cancer. 2021 Mar 19;12(10):2975-2981. doi: 10.7150/jca.56207. eCollection 2021.
To explore the efficacy and safety of lower-dose decitabine in patients with lower-risk MDS, a prospective multicenter phase II study was conducted to compare decitabine with the best supportive care (BSC). Patients diagnosed with lower-risk MDS from September 2013 to August 2018 were assigned to the decitabine group or the BSC group. Decitabine (12 mg/m/day) was administered over 1 hour/day for 5 consecutive days in a 4-week cycle. BSC, including growth factors, transfusion, thalidomide, lenalidomide, and immunosuppressive agents were given consecutively. The endpoints included the proportion of patients who achieved overall response (OR) in the first 2 or 3 courses, event-free survival (EFS), and overall survival (OS). A total of recruited 82 patients were analyzed. In the decitabine group, 65.9% (27/41) achieved OR after 2 or 3 cycles of treatment, compared with 22.0% (9/41) in the BSC group (p <0.01). Besides, 44.0% (11/25) in the decitabine group became independent of RBC/Platelets transfusion, compared with 27.8% (5/18) in the BSC group. Patients with gene mutation and treated with decitabine achieved a higher OR rate, compared with those without gene mutation [72.0% (18/25) vs 11.5% (3/26), p <0.01]. There was no significant difference in the median EFS between the decitabine and BSC groups (20.6 vs 14.3 months respectively, p = 0.665). In the decitabine group, the most significant adverse events were infections of any grades or neutropenic fever (46.3%, 19/41) and one patient (4.2%) died of acute cerebral infarction within 6 weeks of treatment. Lower-dose decitabine demonstrated promising clinical response with acceptable toxicity profiles in patients with low- and intermediate 1-risk MDS. A higher response rate to decitabine was observed in patients with mutated genes. Therefore, lower-dose decitabine can be advocated for patients with low-risk MDS and mutated genes.
为探讨低剂量地西他滨治疗低危骨髓增生异常综合征（MDS）患者的疗效和安全性，开展了一项前瞻性多中心II期研究，比较地西他滨与最佳支持治疗（BSC）。2013年9月至2018年8月诊断为低危MDS的患者被分配至地西他滨组或BSC组。地西他滨（12mg/m²/天）在4周周期内连续5天，每天给药1小时。连续给予BSC，包括生长因子、输血、沙利度胺、来那度胺和免疫抑制剂。终点指标包括在前2或3个疗程中达到总体缓解（OR）的患者比例、无事件生存期（EFS）和总生存期（OS）。共分析了82例招募患者。地西他滨组中，65.9%（27/41）在2或3个周期治疗后达到OR，而BSC组为22.0%（9/41）（p<0.01）。此外，地西他滨组44.0%（11/25）患者不再依赖红细胞/血小板输血，而BSC组为27.8%（5/18）。与未发生基因突变的患者相比，发生基因突变且接受地西他滨治疗的患者达到更高的OR率[72.0%（18/25）对11.5%（3/26），p<0.01]。地西他滨组和BSC组的中位EFS无显著差异（分别为20.6个月和14.3个月，p=0.665）。地西他滨组中，最显著的不良事件为任何级别的感染或中性粒细胞减少性发热（46.3%，19/41），1例患者（4.2%）在治疗6周内死于急性脑梗死。低剂量地西他滨在低危和中危1 MDS患者中显示出有前景的临床反应及可接受的毒性特征。在发生基因突变的患者中观察到对地西他滨更高的反应率。因此，对于低危MDS和发生基因突变的患者可推荐使用低剂量地西他滨。
