New Approaches to Myelodysplastic Syndrome Treatment.

IF 4.7 2区 医学 Q2 ONCOLOGY
Current Treatment Options in Oncology Pub Date : 2022-05-01 Epub Date: 2022-03-23 DOI:10.1007/s11864-022-00965-1
Alexandre Bazinet, Guillermo Montalban Bravo
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引用次数: 8

Abstract

Opinion statement: The treatment of myelodysplastic syndromes (MDS) begins with risk stratification using a validated tool such as the International Prognostic Scoring System (IPSS) or its revised version (IPSS-R). This divides patients into lower- and higher- risk categories. Although treatment objectives in lower-risk MDS (LR-MDS) have traditionally been directed at improving cytopenias (usually anemia) as well as quality of life, recent data supports a potential role for early intervention in delaying transfusion dependency. In addition, careful individualized risk stratification incorporating clinical, cytogenetic, and mutational data might help identify patients at higher-than-expected risk for progression. Given the need for supportive care with red blood cell (RBC) transfusions leading to iron overload, iron chelation should be considered for patients with heavy transfusion requirements at risk for end-organ complications. For patients with LR-MDS and isolated anemia, no high-risk features, and endogenous erythropoietin (EPO) levels below 500 U/L, erythropoiesis-stimulating agents (ESAs) can be attempted to improve anemia. Some LR-MDS patient subgroups may also benefit from specific therapies including luspatercept (MDS with ring sideroblasts), lenalidomide (MDS with deletion 5q), or immunosuppressive therapy (hypocellular MDS). LR-MDS patients failing the above options, or those with multiple cytopenias and/or higher-risk features, can be considered for oral low-dose hypomethylating agent (HMA) therapy. Alternatively, these patients may be enrolled on a clinical trial with promising agents targeting the transforming-growth factor beta (TGF-β) pathway, the hypoxia-inducible factor (HIF) pathway, telomerase activity, inflammatory signaling, or the splicing machinery. In higher-risk MDS (HR-MDS), therapy seeks to modify the natural history of the disease and prolong survival. Eligible patients should be considered for curative allogeneic hematopoietic stem cell transplantation (aHSCT). Despite promising novel combinations, the HMAs azacitidine (AZA) or decitabine (DAC) are still the standard of care for these patients, with intensive chemotherapy-based approaches being a potential option in a small subset of patients. Individuals who fail to respond or progress after HMA experience dismal outcomes and represent a major unmet clinical need. Such patients should be treated as part of a clinical trial if possible. Experimental agents to consider include venetoclax, myeloid cell leukemia 1 (MCL-1) inhibitors, eprenetapopt, CPX-351, immunotherapies (directed towards CD47, TIM3, or CD70), interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors, pevonedistat, seclidemstat, and eltanexor. In this review, we extensively discuss the current landscape of experimental therapies for both LR- and HR-MDS.

骨髓增生异常综合征治疗的新方法。
意见声明:骨髓增生异常综合征(MDS)的治疗始于使用经过验证的工具进行风险分层,如国际预后评分系统(IPSS)或其修订版(IPSS- r)。这将病人分为低危和高危两类。虽然低风险MDS (LR-MDS)的治疗目标传统上是针对改善血细胞减少症(通常是贫血)和生活质量,但最近的数据支持早期干预在延迟输血依赖方面的潜在作用。此外,结合临床、细胞遗传学和突变数据进行仔细的个体化风险分层,可能有助于识别进展风险高于预期的患者。考虑到红细胞(RBC)输注导致铁超载需要支持性护理,对于输注量大且有终末器官并发症风险的患者,应考虑铁螯合治疗。对于低级别mds合并孤立性贫血、无高危特征、内源性促红细胞生成素(EPO)水平低于500 U/L的患者,可尝试使用促红细胞生成素(ESAs)改善贫血。一些低级别MDS患者亚组也可能受益于特异性治疗,包括luspatercept (MDS伴环状铁母细胞)、来那度胺(MDS伴5q缺失)或免疫抑制治疗(低细胞MDS)。以上选择失败的LR-MDS患者,或具有多种细胞减少症和/或高风险特征的患者,可考虑口服低剂量低甲基化剂(HMA)治疗。另外,这些患者可能会参加一项有前景的药物临床试验,这些药物针对转化生长因子β (TGF-β)途径、缺氧诱导因子(HIF)途径、端粒酶活性、炎症信号或剪接机制。在高风险MDS (HR-MDS)中,治疗旨在改变疾病的自然史并延长生存期。符合条件的患者应考虑治疗性异基因造血干细胞移植(aHSCT)。尽管有希望的新组合,HMAs阿扎胞苷(AZA)或地西他滨(DAC)仍然是这些患者的标准护理,以强化化疗为基础的方法是一小部分患者的潜在选择。在HMA治疗后没有反应或进展的个体会经历令人沮丧的结果,并代表一个主要的未满足的临床需求。如果可能的话,这些患者应该作为临床试验的一部分进行治疗。考虑的实验药物包括venetoclax,髓细胞白血病1 (MCL-1)抑制剂,eprenetapopt, CPX-351,免疫疗法(针对CD47, TIM3或CD70),白细胞介素-1受体相关激酶4 (IRAK4)抑制剂,pevonedistat, seclidemstat和eltanexor。在这篇综述中,我们广泛讨论了LR-和HR-MDS的实验治疗的现状。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.10
自引率
0.00%
发文量
113
审稿时长
>12 weeks
期刊介绍: This journal aims to review the most important, recently published treatment option advances in the field of oncology. By providing clear, insightful, balanced contributions by international experts, the journal intends to facilitate worldwide approaches to cancer treatment. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as endocrine tumors, lymphomas, neuro-oncology, and cancers of the breast, head and neck, lung, skin, gastrointestinal tract, and genitourinary region. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. We also provide commentaries from well-known oncologists, and an international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research.
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