利扎布替尼与安慰剂在成人免疫性血小板减少症患者中的安全性和有效性:3期LUNA3研究

IF 23.1 1区 医学 Q1 HEMATOLOGY
Blood Pub Date : 2025-06-12 DOI:10.1182/blood.2024027336
David J Kuter, Waleed Ghanima, Nichola Cooper, Howard A Liebman, Lei Zhang, Yu Hu, Yoshitaka Miyakawa, Wojciech Homenda, Luisa Elena Morales Galindo, Ana Lisa Basquiera, Chuen Wen Tan, Guray Saydam, Marie Luise Hütter-Krönke, Chatree Chai-Adisaksopha, David Gómez-Almaguer, Huy Tran, Ho-Jin Shin, Ademar Dantas da Cunha Junior, Zsolt Lazar, Cristina Pascual Izquierdo, Ilya Kirgner, Elisa Lucchini, Ganna Kuzmina, Michael Fillitz, Sylvain Audia, Minakshi Taparia, Matias Cordoba, Remco Diab, Mengjie Yao, Imene Gouia, Michelle Lee, Ahmed Daak
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引用次数: 0

摘要

利扎布替尼是一种共价的、可逆的BTK抑制剂,具有多种机制,针对关键的免疫性血小板减少症(ITP)疾病的病理生理。在先前治疗过的患有持续性/慢性ITP的成人中进行的3期LUNA3研究评估了口服利扎布替尼400mg bid (n=133)与安慰剂(n=69),持续24周。总体基线时,中位年龄为47岁(范围18-80岁),63%为女性,ITP的中位病程为7.7岁(范围0.3-52.2岁),28%为脾切除术。总体而言(N=202), 85例(64%)利扎布替尼患者和22例(32%)安慰剂患者达到血小板反应(≥50×109/L或30×109/L-)
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study.

Abstract: Rilzabrutinib is a covalent, reversible Bruton tyrosine kinase inhibitor targeting multiple immune thrombocytopenia (ITP)-related mechanisms. The phase 3 LUNA3 study in previously treated adults with persistent/chronic ITP evaluated oral rilzabrutinib 400 mg twice daily (n = 133) vs placebo (n = 69) for 24 weeks. At baseline overall, median age was 47 years, 63% female, 7.7 year median ITP duration, and 28% prior splenectomy. Overall (N = 202), 85 (64%) rilzabrutinib and 22 (32%) placebo patients achieved platelet response (≥50 × 109/L or 30 × 109/L to <50 × 109/L and doubled from baseline) during the first 12 weeks and were eligible to continue. The primary end point, durable platelet response (platelet count ≥50 × 109/L for ≥two-thirds of ≥8 of the last 12 of 24 weeks without rescue therapy), was observed in 31 (23%) rilzabrutinib vs 0 placebo patients (P < .0001). All secondary efficacy end points were significantly superior for rilzabrutinib (P < .05). Median time to first platelet response was 15 days in rilzabrutinib responders. Rilzabrutinib significantly reduced rescue therapy use by 52% (P = .0007) and improved week 25 bleeding scores (P = .0006). Improved physical fatigue was sustained from week 13 (P = .01) through 25 (P = .0003). Treatment-related adverse events were mainly grade 1/2. One rilzabrutinib patient with multiple risk factors had serious treatment-related grade 3 peripheral embolism (lower left leg), and another died from unrelated pneumonia. Rilzabrutinib in patients who failed multiple previous ITP therapies showed rapid and durable platelet response, reduced rescue medication and bleeding, improved physical fatigue, and favorable safety. Trial registration: www.clinicaltrials.gov (#NCT04562766) and www.clinicaltrialsregister.eu (#2020-002063-60).

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来源期刊
Blood
Blood 医学-血液学
CiteScore
23.60
自引率
3.90%
发文量
955
审稿时长
1 months
期刊介绍: Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.
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