Usuki Kensuke
Department of Hematology, Medical Center Tokyo.
Rinsho Ketsueki. 2022;63(9):1099-1106. doi: 10.11406/rinketsu.63.1099.
Several novel myelodysplastic syndromes (MDS) treatment drugs are being developed, and luspatercept and oral hypomethylating medicines have already been licensed in the United States and other countries. Luspatercept is a ligand trap that inhibits SMAD2/3 signals by combining the extracellular domain of the activin type IIA receptor with the human immunoglobulin G1 Fc domain. In the phase 2 study for low-risk MDS, the hematological improvement-erythroid (HI-E) was found in 63% of patients, and in the phase 3 study for transfusion-dependent low-risk MDS with ring sideroblasts, 38% of patients achieved transfusion independence. A combination of oral decitabine with oral cedazuridine, an inhibitor of cytidine deaminase, which metabolizes decitabine, demonstrated pharmacological equivalence with intravenous decitabine and has overall response rates of 60% and 43% for high-risk MDS in phase 2 and 3 trials, respectively. Furthermore, oral azacitidine and its combination with oral cedazuridine have been under development.
几种新型骨髓增生异常综合征（MDS）治疗药物正在研发中，且罗特西普和口服低甲基化药物已在美国及其他国家获批。罗特西普是一种配体陷阱，通过将激活素IIA型受体的胞外域与人免疫球蛋白G1 Fc结构域结合来抑制SMAD2/3信号。在针对低危MDS的2期研究中，63%的患者出现血液学改善-红系（HI-E），而在针对伴有环形铁粒幼细胞的输血依赖型低危MDS的3期研究中，38%的患者实现了输血独立。口服地西他滨与胞苷脱氨酶抑制剂口服塞扎苷联合使用，胞苷脱氨酶可代谢地西他滨，该联合用药在药理学上等同于静脉用地西他滨，在2期和3期试验中，高危MDS的总缓解率分别为60%和43%。此外，口服阿扎胞苷及其与口服塞扎苷的联合用药也在研发中。
