Department of Medicine, University of Chicago, Chicago, IL, USA.
Section of Hematology-Oncology, Department of Medicine, University of Chicago, 5841 S Maryland Avenue MC 2115, Chicago, IL, 60637, USA.
Curr Treat Options Oncol. 2024 Jun;25(6):752-768. doi: 10.1007/s11864-024-01217-0. Epub 2024 May 30.
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.
大多数低危骨髓增生异常综合征 (MDS) 患者会出现或发展为贫血。 MDS 中的贫血与生活质量下降有关，并且可能与无进展生存期和总生存期缩短相关。在本次最新综述中，我们总结了当前用于识别低危 MDS（LR-MDS）的风险分层方法、疾病的自然史以及有意义的临床终点。贫血性 LR-MDS 的治疗领域也在迅速发展；我们综述了支持性治疗、促红细胞生成素刺激剂、来那度胺、芦曲泊帕、低甲基化剂（HMAs）和免疫抑制治疗（IST）在贫血性 LR-MDS 管理中的作用。在 5q 缺失（del5q）综合征患者中，来那度胺具有疗效和持久缓解作用。对于不需要治疗的无 del5q 患者，治疗方法受血清促红细胞生成素（EPO）水平、SF3B1 突变状态和环形铁幼粒细胞状态的影响。鉴于 III 期 COMMANDS 试验的数据，我们在那些具有 SF3B1 突变或环形铁幼粒细胞并且 EPO 水平 < 500 U/L 的患者中使用芦曲泊帕；在没有 SF3B1 突变或环形铁幼粒细胞的患者中，芦曲泊帕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≥500 U/L 或以前接受过治疗的患者，目前尚无明确的治疗标准。对于没有以前使用过芦曲泊帕的患者，如果存在 SF3B1 突变或环形铁幼粒细胞，可以考虑使用。其他选择包括 HMAs 或 IST；III 期 IMERGE 试验支持端粒酶抑制剂imetelstat 在这种情况下的疗效，未来它也可能成为一种标准选择。
