帕沙利西治疗原发性自身免疫性溶血性贫血:2期开放标签研究结果。

IF 10.1 1区 医学 Q1 HEMATOLOGY American Journal of Hematology Pub Date : 2024-12-01 Epub Date: 2024-10-22 DOI:10.1002/ajh.27493
Wilma Barcellini, Fabrizio Pane, Andrea Patriarca, Irina Murakhovskaya, Louis Terriou, Maria T DeSancho, Wahid T Hanna, Lance Leopold, Erica Rappold, Ke Szeto, Shaoceng Wei, Ulrich Jäger
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引用次数: 0

摘要

自身免疫性溶血性贫血(AIHA)是一组以红细胞溶血为特征的获得性自身免疫性疾病。在一项二期开放标签多中心研究中,患有温性AIHA、冷凝集素病或混合型AIHA的成人每天口服一次1.0或2.5毫克帕沙利西(选择性磷脂酰肌醇3-激酶δ抑制剂),疗程12周,然后延长疗程。允许增加剂量(因AIHA恶化)或减少剂量(因耐受性)。主要疗效终点是在第6-12周的任何一次就诊中,完全应答(血红蛋白[Hgb]≥12 g/dL)或部分应答(血红蛋白[Hgb]10-12 g/dL或比基线增加≥2 g/dL)且非输血所致的患者比例。在 25 名入组患者(中位年龄 63 岁)中,有 16 人(64%)在第 6-12 周达到了部分或完全 Hgb 反应。52.0%的患者在第1周时出现应答,在第6-12周期间病情逐渐好转,并在延长期内持续应答。温性 AIHA 患者的应答率高于其他类型患者(75.0% 对 44.4%)。在第6周和第12周,慢性疾病治疗功能评估-疲劳评分出现了有临床意义的改善。所有患者都出现了治疗突发不良事件(TEAEs),最常见的是腹泻(32.0%)和发热(28.0%)。13名患者(52.0%)发生了≥3级TEAE。11名患者(44.0%)出现了可能与治疗有关的TEAE。无须减少剂量;6 名患者(24%)因 TEAE 而停药。总之,帕沙利西耐受性良好,第 1 周时血红蛋白反应显著改善,延长期反应持久。临床试验注册:该试验已在 ClinicalTrials.gov (NCT03538041) 上注册。
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Parsaclisib for the treatment of primary autoimmune hemolytic anemia: Results from a phase 2, open-label study.

Autoimmune hemolytic anemia (AIHA) is a group of acquired autoimmune disorders characterized by red blood cell hemolysis. In a phase 2, open-label, multicenter study, adults with warm AIHA, cold agglutinin disease, or mixed-type AIHA were administered once-daily 1.0 or 2.5 mg parsaclisib (selective phosphoinositide 3-kinase δ inhibitor) orally for 12 weeks, followed by an extension period. Dose increases (for AIHA worsening) or decreases (for tolerability) were permitted. Primary efficacy endpoint was the proportion of patients with complete (≥12 g/dL hemoglobin [Hgb]) or partial (10-12 g/dL Hgb or ≥2 g/dL increase from baseline) response at any visit during weeks 6-12 not attributable to transfusion. Among 25 enrolled patients (median age, 63 y), 16 (64%) achieved a partial or complete Hgb response during weeks 6-12. Responses were observed by week 1 in 52.0% of patients with incremental improvements during weeks 6-12 and sustained responses during the extension period. Responses were higher among patients with warm AIHA versus other types (75.0% vs. 44.4%). Clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue scores were observed at weeks 6 and 12. All patients had treatment-emergent adverse events (TEAEs), most commonly diarrhea (32.0%) and pyrexia (28.0%). Grade ≥3 TEAEs occurred in 13 patients (52.0%). TEAEs considered possibly related to treatment occurred in 11 patients (44.0%). No dose reductions were required; six patients (24%) discontinued for a TEAE. In summary, parsaclisib was well tolerated and resulted in substantial improvements in Hgb response at week 1, with durable responses through the extension period. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT03538041).

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来源期刊
CiteScore
15.70
自引率
3.90%
发文量
363
审稿时长
3-6 weeks
期刊介绍: The American Journal of Hematology offers extensive coverage of experimental and clinical aspects of blood diseases in humans and animal models. The journal publishes original contributions in both non-malignant and malignant hematological diseases, encompassing clinical and basic studies in areas such as hemostasis, thrombosis, immunology, blood banking, and stem cell biology. Clinical translational reports highlighting innovative therapeutic approaches for the diagnosis and treatment of hematological diseases are actively encouraged.The American Journal of Hematology features regular original laboratory and clinical research articles, brief research reports, critical reviews, images in hematology, as well as letters and correspondence.
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