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.

中文翻译：

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Parsaclisib 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


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 2 期、开放标签、多中心研究中，患有温型 AIHA、冷凝集素病或混合型 AIHA 的成人每天一次口服 1.0 或 2.5 mg parsaclisib（选择性磷酸肌醇 3-激酶δ抑制剂），持续 12 周，然后延长期。允许增加剂量（针对 AIHA 恶化）或减少剂量（针对耐受性）。主要疗效终点是在第 6-12 周的任何访视中完全 （≥12 g/dL 血红蛋白 [Hgb]）或部分 （10-12 g/dL Hgb 或较基线增加 ≥2 g/dL） 反应的患者比例，不能归因于输血。在 25 名入组患者 （中位年龄，63 岁） 中，16 名 （64%） 在第 6-12 周内达到部分或完全 Hgb 反应。到 1 周时，52.0% 的患者观察到反应，第 6-12 周有增量改善，延长期有持续反应。温型 AIHA 患者的反应高于其他类型的 （75.0% vs. 44.4%）。在第 6 周和第 12 周观察到慢性病治疗功能评估-疲劳评分的临床意义改善。所有患者均出现治疗中出现的不良事件 （TEAE），最常见的是腹泻 （32.0%） 和发热 （28.0%）。13 例患者 （52.0%） 发生 ≥3 级 TEAE。被认为可能与治疗相关的 TEAE 发生在 11 例患者 （44.0%） 中。不需要减少剂量;6 例患者 （24%） 因 TEAE 而停药。总之，parsaclisib 耐受性良好，并在第 1 周导致 Hgb 反应显着改善，在整个延长期内反应持久。