A critical review of belumosudil in adult and pediatric patients with chronic graft-versus-host disease.

IF 3.9 3区 医学 Q2 IMMUNOLOGY
Amandeep Salhotra, Karamjeet Sandhu, James O'Hearn, Haris Ali, Ryotaro Nakamura, Badri G Modi
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引用次数: 1

Abstract

Introduction: Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is the main cause of late non-relapse mortality (NRM). Three new agents are now approved to treat cGVHD, of which belumosudil has a unique and dual mechanism of action of i) targeting the Rho-GTPase-associated coiled-coil kinase 2 (ROCK2) in T helper follicular cells (TFH) and TH17 cells, this results in downregulation of proinflammatory cytokines (interleukin -21 and 17), the former in a STAT3-dependent mechanism, ii) inhibition of tissue fibrosis by targeting stress-induced polymerization of G-actin fibrils by inhibiting the Rho-ROCK-MRTF pathway.

Areas covered: In this review we describe the epidemiology of cGVHD, its cardinal symptoms, preventive and therapeutic options, including second-line approved therapies in the United States (US). Clinical trial data that led to approval of belumosudil is discussed, in addition to the clinical scenarios in which the approved drugs may be most applicable.

Expert opinion: Belumosudil is approved for treatment of adult and pediatric patients ≥ 12 years with cGVHD after failing two lines of therapy based on results of the ROCKstar study that showed high overall response rates (ORR), favorable adverse effect profiles, and low rates of severe infections. With the availability of three new agents for treatment of cGVHD, treating physicians have more therapeutic options for patients and have additional options of development new clinical trials using a combination of recently approved drugs.

白莫硫地尔在成人和儿童慢性移植物抗宿主病患者中的应用综述
慢性移植物抗宿主病(Chronic graft- anti -host disease, cGVHD)是异基因造血细胞移植(allogeneic hematopoietic cell transplantation, alloo - hct)的一种并发症,是晚期非复发性死亡(non-relapse mortality, NRM)的主要原因。三个新的代理现在批准治疗cGVHD belumosudil有独特的和双我的作用机制)针对Rho-GTPase-associated卷曲螺旋激酶2 (ROCK2) T辅助滤泡细胞(TFH)和TH17细胞,促炎细胞因子的差别这导致对这些-21年(白介素17),前者STAT3-dependent机制,2)抑制组织纤维化的目标压力诱导聚合G-actin纤维通过抑制Rho-ROCK-MRTF通路。涵盖领域:在本综述中,我们描述了cGVHD的流行病学、主要症状、预防和治疗方案,包括美国批准的二线治疗方法。讨论了导致批准白莫硫地尔的临床试验数据,以及批准的药物可能最适用的临床情况。专家意见:基于ROCKstar研究的结果显示,高总缓解率(ORR)、良好的不良反应概况和低严重感染率,Belumosudil被批准用于治疗≥12年cGVHD的成人和儿童患者。随着三种用于治疗cGVHD的新药物的可用性,治疗医生为患者提供了更多的治疗选择,并有了使用最近批准的药物组合进行新的临床试验的额外选择。
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来源期刊
CiteScore
7.60
自引率
2.30%
发文量
221
审稿时长
6-12 weeks
期刊介绍: Expert Review of Clinical Immunology (ISSN 1744-666X) provides expert analysis and commentary regarding the performance of new therapeutic and diagnostic modalities in clinical immunology. Members of the International Editorial Advisory Panel of Expert Review of Clinical Immunology are the forefront of their area of expertise. This panel works with our dedicated editorial team to identify the most important and topical review themes and the corresponding expert(s) most appropriate to provide commentary and analysis. All articles are subject to rigorous peer-review, and the finished reviews provide an essential contribution to decision-making in clinical immunology. Articles focus on the following key areas: • Therapeutic overviews of specific immunologic disorders highlighting optimal therapy and prospects for new medicines • Performance and benefits of newly approved therapeutic agents • New diagnostic approaches • Screening and patient stratification • Pharmacoeconomic studies • New therapeutic indications for existing therapies • Adverse effects, occurrence and reduction • Prospects for medicines in late-stage trials approaching regulatory approval • Novel treatment strategies • Epidemiological studies • Commentary and comparison of treatment guidelines Topics include infection and immunity, inflammation, host defense mechanisms, congenital and acquired immunodeficiencies, anaphylaxis and allergy, systemic immune diseases, organ-specific inflammatory diseases, transplantation immunology, endocrinology and diabetes, cancer immunology, neuroimmunology and hematological diseases.
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