Abstract:
UNASSIGNED: A majority of patients with lower-risk myelodysplastic syndrome (MDS) will present with or develop anemia. Anemia in MDS is associated with decreased quality of life and may correlate with decreased progression-free survival and overall survival. In this state of the art review we summarize current risk stratification approaches to identify lower-risk MDS (LR-MDS), the natural history of the disease, and meaningful clinical endpoints. The treatment landscape of LR-MDS with anemia is also rapidly evolving; we review the role of supportive care, erythropoietin stimulating agents, lenalidomide, luspatercept, hypomethylating agents (HMAs), and immunosuppressive therapy (IST) in the management of LR-MDS with anemia. In patients with deletion 5q (del5q) syndrome lenalidomide has both efficacy and durability of response. For patients without del5q who need treatment, the management approach is impacted by serum erythropoietin (EPO) level, SF3B1 mutation status, and ring sideroblast status. Given the data from the Phase III COMMANDS trial, we utilize luspatercept in those with SF3B1 mutation or ring sideroblasts that have an EPO level < 500 U/L; in patients without an SF3B1 mutation or ring sideroblasts there is equipoise between luspatercept and use of an erythropoietin stimulating agent (ESA). For patients who have an EPO level ≥ 500 U/L or have been previously treated there is not a clear standard of care. For those without previous luspatercept exposure it can be considered particularly if there is an SF3B1 mutation or the presence of ring sideroblasts. Other options include HMAs or IST; the Phase III IMERGE trial supports the efficacy of the telomerase inhibitor imetelstat in this setting and this may become a standard option in the future as well.
摘要:
■大多数患有低危骨髓增生异常综合征(MDS)的患者会出现或发展为贫血。MDS患者的贫血与生活质量下降相关,可能与无进展生存期和总生存期下降相关。在这篇最新的综述中,我们总结了当前的风险分层方法来识别低风险MDS(LR-MDS),疾病的自然史,和有意义的临床终点。LR-MDS贫血的治疗前景也在迅速发展;我们回顾了支持性护理的作用,促红细胞生成素刺激剂,来那度胺,Luspatercept,低甲基化剂(HMA),和免疫抑制治疗(IST)在治疗LR-MDS伴贫血中的应用。在缺失5q(del5q)综合征患者中,来那度胺具有疗效和持久性反应。对于需要治疗的没有del5q的患者,管理方法受到血清促红细胞生成素(EPO)水平的影响,SF3B1突变状态,和环sideroblast状态。鉴于第三阶段命令试验的数据,我们将luspatercept用于SF3B1突变或EPO水平<500U/L的环侧分生细胞;在无SF3B1突变或环侧分生细胞的患者中,luspatercept与使用促红细胞生成素刺激剂(ESA)之间存在平衡.对于EPO水平≥500U/L或以前接受过治疗的患者,没有明确的护理标准。对于那些以前没有luspatercept暴露的人,如果存在SF3B1突变或存在环铁粒细胞,则可以特别考虑。其他选择包括HMA或IST;IMERGEIII期试验支持端粒酶抑制剂imetelstat在这种情况下的功效,并且将来也可能成为标准选择。