Impact of cytopenias and early versus late treatment with ruxolitinib in patients with steroid-refractory acute or chronic graft-versus-host disease.

IF 4.5 2区 医学 Q1 HEMATOLOGY Bone Marrow Transplantation Pub Date : 2024-11-06 DOI:10.1038/s41409-024-02445-6
Zahra Mahmoudjafari, Valkal Bhatt, John Galvin, Zhenyi Xue, Robert Zeiser, Franco Locatelli, Gérard Socié, Mohamad Mohty
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Abstract

REACH2 and REACH3 were randomized, multicenter, open-label phase 3 studies comparing the selective Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib versus investigators' choice of best available therapy (BAT) in steroid-refractory (SR) acute (REACH2) or chronic (REACH3) graft-versus-host disease (aGVHD/cGVHD). Moderate-severe aGVHD/cGVHD can progress rapidly; thus, key clinical considerations driving management of patients with SR-aGVHD/SR-cGVHD are prompt treatment initiation and concomitant cytopenias. These post hoc analyses of REACH2/REACH3 describe the impact of timing of treatment initiation after SR-aGVHD/SR-cGVHD diagnosis and development of concomitant cytopenias on treatment outcomes. Ruxolitinib initiation within 3 days from SR-aGVHD diagnosis yielded an extended duration of response and higher Day 28 complete response rates compared with initiation ≥7 days after SR-aGVHD diagnosis (median 178 vs 167 days and 36.6% vs 25.0%, respectively). For patients with SR-cGVHD, Week 24 overall response was not impacted by time to treatment (54.5% vs 42.6% for <14 vs >28 days). Clinically relevant cytopenias were manageable, allowing for maintenance of dose intensity (median 20 mg/d), and did not impact the favorable efficacy outcomes from ruxolitinib treatment. This analysis highlights the practical importance of considering earlier ruxolitinib initiation after SR diagnosis in GVHD and the benefits of ruxolitinib treatment compared with BAT even for patients with cytopenias.

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类固醇难治性急性或慢性移植物抗宿主病患者细胞减少症以及早期与晚期使用鲁索利替尼治疗的影响。
REACH2和REACH3是随机、多中心、开放标签的3期研究,比较了选择性Janus激酶(JAK)1/JAK2抑制剂鲁索利替尼与研究者选择的最佳可用疗法(BAT)在类固醇难治性(SR)急性(REACH2)或慢性(REACH3)移植物抗宿主疾病(aGVHD/cGVHD)中的疗效。中度重度 aGVHD/cGVHD 病情发展迅速;因此,对 SR-aGVHD/SR-cGVHD 患者进行管理的关键临床因素是及时开始治疗和并发细胞减少症。REACH2/REACH3的这些事后分析描述了SR-aGVHD/SR-cGVHD确诊后开始治疗的时机以及并发细胞减少症对治疗结果的影响。与SR-aGVHD确诊后≥7天开始治疗相比,在SR-aGVHD确诊后3天内开始Ruxolitinib治疗可延长应答持续时间,第28天完全应答率更高(中位数分别为178天对167天,36.6%对25.0%)。对于SR-cGVHD患者,第24周的总体反应不受治疗时间的影响(54.5%对42.6%,28天)。临床相关的细胞减少是可控的,可以维持剂量强度(中位数为20毫克/天),不会影响芦可利替尼治疗的良好疗效。这项分析强调了在GVHD患者确诊SR后考虑尽早启动鲁索利替尼治疗的实际重要性,以及与BAT相比鲁索利替尼治疗的益处,即使对有细胞减少症的患者也是如此。
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来源期刊
Bone Marrow Transplantation
Bone Marrow Transplantation 医学-免疫学
CiteScore
8.40
自引率
8.30%
发文量
337
审稿时长
6 months
期刊介绍: Bone Marrow Transplantation publishes high quality, peer reviewed original research that addresses all aspects of basic biology and clinical use of haemopoietic stem cell transplantation. The broad scope of the journal thus encompasses topics such as stem cell biology, e.g., kinetics and cytokine control, transplantation immunology e.g., HLA and matching techniques, translational research, and clinical results of specific transplant protocols. Bone Marrow Transplantation publishes 24 issues a year.
期刊最新文献
Measurable residual disease testing and allogeneic hematopoietic cell transplantation for AML: adapting Pre-MEASURE to clinical practice. High-dose chemotherapy with autologous haematopoietic stem cell transplantation in patients with isolated vitreoretinal lymphoma: a LOC network study. Immunological reconstitution and infections after alloHCT - a comparison between post-transplantation cyclophosphamide, ATLG and non-ATLG based GvHD prophylaxis. Belumosudil combination therapy for chronic graft-versus-host-disease in real-world clinical practice. Successful allogeneic CD34+ hematopoietic stem cell boost for prolonged cytopenias following CAR T-cell therapy in B-cell acute lymphoblastic leukemia. On behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).
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