Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study.
Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study.
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DOI：
10.1182/blood.2021012021
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发表时间：
2021-12-02
期刊：
影响因子：
20.3
通讯作者：
Pavletic S
中科院分区：
文献类型：
--
作者：
Cutler C;Lee SJ;Arai S;Rotta M;Zoghi B;Lazaryan A;Ramakrishnan A;DeFilipp Z;Salhotra A;Chai-Ho W;Mehta R;Wang T;Arora M;Pusic I;Saad A;Shah NN;Abhyankar S;Bachier C;Galvin J;Im A;Langston A;Liesveld J;Juckett M;Logan A;Schachter L;Alavi A;Howard D;Waksal HW;Ryan J;Eiznhamer D;Aggarwal SK;Ieyoub J;Schueller O;Green L;Yang Z;Krenz H;Jagasia M;Blazar BR;Pavletic S
慢性移植物抗宿主病（CGVHD）是同种异体造血干细胞移植后发病率和晚期死亡率的主要原因。他们需要第三次或以后的治疗。对立体的ruxolitinib和ibrutinib的耐火性。
Belumosudil是一种选择性Rock2抑制剂，在经过大量预处理的受试者中耐受性良好，44％的继续治疗超过1年。
Belumosudil在SR CGVHD患者中表现出效率，在所有器官和ibrutinib/ruxolitinib衰竭之后的反应。
Belumosudil是一种研究性的口服选择性抑制剂，用于含卷曲的蛋白激酶2（Rock2），通过下调STAT3的下调17型和卵泡T辅助细胞，并通过STAT5的上调来增强调节性T细胞。与慢性移植物抗宿主病（CGVHD）一起，这是同种异体造血细胞移植后发病率和晚期非解散死亡率的主要原因。这一阶段2随机多中心注册研究评估了Belumosudil 200 mg（n = 66）和200 mg每天两次（n = 66）的CGVHD受试者接受了2至5个先前的治疗。速率（ORR）随访时间为14个月。在所有受影响的器官中，所有受试者的响应率都在所有受试者中，所有受试者的中位数为54％。每天和200毫克的受试者分别在59％和62％的受试者中与接受皮质类固醇的CGVHD患者和其他免疫抑制剂的预期相一致。与药物相关的AES。 www.clinicaltrials.gov as＃nct03640481。
Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and late mortality after allogeneic hematopoietic stem cell transplantation. Cutler and colleagues report on a randomized phase 2 clinical trial of belumosudil, an oral ROCK2 inhibitor, in 132 patients with cGVHD requiring third- or later-line therapy. They found that treatment with 200 mg of belumosudil daily induces responses in 74% of patients, including those with cGVHD refractory to steroids, ruxolitinib, and ibrutinib. These data form the basis for this agent’s recent approval by the US Food and Drug Administration. Belumosudil, a selective ROCK2 inhibitor, was well tolerated in heavily pretreated subjects, with 44% continuing treatment beyond 1 year. Belumosudil demonstrated efficacy in patients with SR cGVHD, with responses in all organs and after failure of ibrutinib/ruxolitinib. Belumosudil, an investigational oral selective inhibitor of Rho-associated coiled-coil–containing protein kinase 2 (ROCK2), reduces type 17 and follicular T helper cells via downregulation of STAT3 and enhances regulatory T cells via upregulation of STAT5. Belumosudil may effectively treat patients with chronic graft-versus-host disease (cGVHD), a major cause of morbidity and late nonrelapse mortality after an allogeneic hematopoietic cell transplant. This phase 2 randomized multicenter registration study evaluated belumosudil 200 mg daily (n = 66) and 200 mg twice daily (n = 66) in subjects with cGVHD who had received 2 to 5 prior lines of therapy. The primary end point was best overall response rate (ORR). Duration of response (DOR), changes in Lee Symptom Scale score, failure-free survival, corticosteroid dose reductions, and overall survival were also evaluated. Overall median follow-up was 14 months. The best ORR for belumosudil 200 mg daily and 200 mg twice daily was 74% (95% confidence interval [CI], 62-84) and 77% (95% CI, 65-87), respectively, with high response rates observed in all subgroups. All affected organs demonstrated complete responses. The median DOR was 54 weeks; 44% of subjects have remained on therapy for ≥1 year. Symptom reduction with belumosudil 200 mg daily and 200 mg twice daily was reported in 59% and 62% of subjects, respectively. Adverse events (AEs) were consistent with those expected in patients with cGVHD receiving corticosteroids and other immunosuppressants. Sixteen subjects (12%) discontinued belumosudil because of possible drug-related AEs. Belumosudil, a promising therapy for cGVHD, was well tolerated with clinically meaningful responses. This trial was registered at www.clinicaltrials.gov as #NCT03640481.
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影响因子：
4.8
作者：
Treister, N.;Chai, X.;Cutler, C.
通讯作者：
Cutler, C.
影响因子：
4.3
作者：
Wolff, Daniel;Schleuning, Michael;Holler, Ernst
通讯作者：
Holler, Ernst
DOI：
10.1007/s12032-018-1127-2
发表时间：
2018-04-25
期刊：
Medical oncology (Northwood, London, England)
影响因子：
--
作者：
Afram G;Simón JAP;Remberger M;Caballero-Velázquez T;Martino R;Piñana JL;Ringden O;Esquirol A;Lopez-Corral L;Garcia I;López-Godino O;Sierra J;Caballero D;Ljungman P;Vazquez L;Hägglund H
通讯作者：
Hägglund H
DOI：
10.1016/j.bbmt.2015.02.025
发表时间：
2015-06
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Lee SJ;Wolff D;Kitko C;Koreth J;Inamoto Y;Jagasia M;Pidala J;Olivieri A;Martin PJ;Przepiorka D;Pusic I;Dignan F;Mitchell SA;Lawitschka A;Jacobsohn D;Hall AM;Flowers ME;Schultz KR;Vogelsang G;Pavletic S
通讯作者：
Pavletic S
DOI：
10.1053/bbmt.2002.v8.pm12234170
发表时间：
2002-01-01
影响因子：
4.3
作者：
Lee, SJ;Cook, EF;Antin, JH
通讯作者：
Antin, JH