Madanat Yazan F, Xie Zhuoer, Zeidan Amer M
Simmons Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Expert Rev Hematol. 2023 Jan;16(1):51-63. doi: 10.1080/17474086.2023.2166923. Epub 2023 Jan 12.
Myelodysplastic syndromes (MDS) are heterogeneous group of clonal hematopoietic stem cell neoplasms that have limited approved treatment options. Multiple novel agents are currently being tested in a clinical trial setting. From a therapeutic perspective, MDS is generally divided into lower-risk and higher-risk disease. In this review, we summarize some of the most prominent novel agents currently in development.
This review focuses on select clinical trials in both lower- and higher-risk MDS, elucidating the mechanisms of action and rationale for drug combinations and summarizing early safety and efficacy data using novel agents in MDS.
Advances in understanding the innate immune system, telomere biology, as well as genomic drivers of the disease have led to the development of multiple novel agents that are currently in late stages of clinical development in MDS. Imetelstat is being tested in lower-risk disease and the phase III clinical trial recently completed accrual. Magrolimab, sabatolimab, and venetoclax in addition to novel oral hypomethylating agents (HMA) are being investigated in higher-risk MDS. These advances will hopefully bring better treatment options to patients and lead to a shift in the treatment paradigm. Post HMA therapy remains an area of dire unmet need.
骨髓增生异常综合征（MDS）是一组异质性的克隆性造血干细胞肿瘤，其获批的治疗选择有限。目前多种新型药物正在临床试验中进行测试。从治疗角度来看，MDS通常分为低风险和高风险疾病。在本综述中，我们总结了一些目前正在研发的最突出的新型药物。
本综述重点关注低风险和高风险MDS的部分临床试验，阐明药物联合使用的作用机制和原理，并总结在MDS中使用新型药物的早期安全性和有效性数据。
在对先天性免疫系统、端粒生物学以及该疾病的基因组驱动因素的理解方面取得的进展，已促成了多种新型药物的研发，这些药物目前正处于MDS临床开发的后期阶段。Imetelstat正在低风险疾病中进行测试，III期临床试验最近已完成入组。除新型口服去甲基化药物（HMA）外，Magrolimab、sabatolimab和维奈克拉正在高风险MDS中进行研究。这些进展有望为患者带来更好的治疗选择，并导致治疗模式的转变。HMA治疗后仍有一个迫切未得到满足的需求领域。
