METHODS: Patients with PNH and hemoglobin ≥10.0 g/dL at baseline of PADDOCK (N = 6), PRINCE (N = 8), and PEGASUS (N = 11) were included. Before receiving pegcetacoplan, PADDOCK and PRINCE patients were C5i-naive; PEGASUS patients had hemoglobin <10.5 g/dL despite stably dosed eculizumab. Hemoglobin concentrations, percentages of patients with concentrations ≥12 g/dL, and sex-specific normalization were assessed at baseline and after 16 weeks of pegcetacoplan, as were absolute reticulocyte counts (ARCs) and normalization and fatigue scores and normalization.
RESULTS: From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 [0.4] to 12.7 [1.1] g/dL; PRINCE: 11.3 [1.0] to 14.0 [1.3] g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 [0.2] to 12.8 [2.6] g/dL). Percentage of patients with hemoglobin ≥12 g/dL increased (PADDOCK: 0 to 60.0% [3 of 5 patients]; PRINCE: 25.0% [2 of 8] to 87.5% [7 of 8]; PEGASUS: 0 to 72.7% [8 of 11]). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation.
CONCLUSIONS: Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan.
BACKGROUND: Trial registration numbers: PADDOCK (NCT02588833), PRINCE (NCT04085601; EudraCT, 2018-004220-11), PEGASUS (NCT03500549).
方法:在PADDOCK基线时PNH和血红蛋白≥10.0g/dL的患者(N=6),王子(N=8),包括PEGASUS(N=11)。在收到pegcetacoplan之前,PADDOCK和PRINCE患者未接受C5i治疗;PEGASUS患者的血红蛋白<10.5g/dL,尽管依库珠单抗剂量稳定。血红蛋白浓度,浓度≥12g/dL的患者百分比,在基线和pegcetacoplan16周后评估性别特异性正常化,网织红细胞绝对计数(ARCs)和正常化以及疲劳评分和正常化.
结果:从基线到第16周,未接受C5i治疗的患者的平均(SD)血红蛋白浓度增加(PADDOCK:10.5[0.4]至12.7[1.1]g/dL;PRINCE:11.3[1.0]至14.0[1.3]g/dL)和具有次优依库珠单抗反应的患者(PEGASUS:10.2[0.2]至12.8血红蛋白≥12g/dL的患者百分比增加(PADDOCK:0至60.0%[5例患者中的3例];PRINCE:25.0%[2/8]至87.5%[7/8];PEGASUS:0至72.7%[8/11])。第16周时性别特异性血红蛋白正常化的发生率为40.0%(5个中的2个)(PADDOCK),62.5%(5/8)(王子),和63.6%(11个中的7个)(PEGASUS)。在所有研究中,平均ARCs从高于正常下降到正常,ARC正常化增加。慢性病治疗的平均功能评估-疲劳评分从低到高于或接近正常。两名患者出现严重不良事件(PEGASUS:术后败血症,突破性溶血);突破性溶血在没有停止研究的情况下解决。
结论:患有PNH和轻度/中度贫血的C5i初治或尽管依库珠单抗治疗仍未达到最佳血红蛋白浓度的患者,在开始或改用pegcetacoplan后,血液学结果改善,疲劳减轻。
背景:试验注册号:PADDOCK(NCT02588833),王子(NCT04085601;EudraCT,2018-004220-11),PEGASUS(NCT03500549)。