对于接受过依库珠单抗或对补体抑制剂无反应的阵发性夜间血红蛋白尿症且伴有轻度或中度贫血（血红蛋白≥10 g/dL）的患者，培戈洛肽可改善血液学标志物并减轻疲劳。

Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin ≥10 g/dL) who had received eculizumab or were naive to complement inhibitors.

机构信息

Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.

Center for Integrated Oncology (CIO), Dusseldorf (ABCD), Aachen, Bonn, Cologne, Germany.

出版信息

PLoS One. 2024 Jul 29;19(7):e0306407. doi: 10.1371/journal.pone.0306407. eCollection 2024.

DOI:10.1371/journal.pone.0306407

PMID:39079163

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11285951/

Abstract

BACKGROUND

Although complement component 5 inhibitors (C5is) eculizumab and ravulizumab improve paroxysmal nocturnal hemoglobinuria (PNH) outcomes, patients may experience persistent anemia. This post hoc analysis investigated whether the complement component 3-targeted therapy pegcetacoplan also improved hematologic outcomes and reduced fatigue in patients with PNH and mild/moderate anemia.

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.

CONCLUSION

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.

TRIAL REGISTRATION

Trial registration numbers: PADDOCK (NCT02588833), PRINCE (NCT04085601; EudraCT, 2018-004220-11), PEGASUS (NCT03500549).

摘要

背景

尽管补体成分 5 抑制剂（C5i）依库珠单抗和拉维珠单抗改善了阵发性夜间血红蛋白尿（PNH）的预后，但患者可能仍会出现持续性贫血。本事后分析旨在研究补体成分 3 靶向治疗培塞利珠单抗是否也能改善 PNH 合并轻度/中度贫血患者的血液学结局并减轻疲劳。

方法

在 PADDOCK（N=6）、PRINCE（N=8）和 PEGASUS（N=11）研究中，纳入基线时血红蛋白≥10.0 g/dL 的 PNH 患者。在接受培塞利珠单抗治疗前，PADDOCK 和 PRINCE 患者均为 C5i 初治患者；PEGASUS 患者尽管接受了稳定剂量的依库珠单抗治疗，但血红蛋白仍<10.5 g/dL。评估了基线时和接受培塞利珠单抗治疗 16 周后血红蛋白浓度、浓度≥12 g/dL 的患者比例、性别特异性血红蛋白正常化情况，以及绝对网织红细胞计数（ARC）和正常化、疲劳评分和正常化情况。

结果

从基线到第 16 周，C5i 初治患者（PADDOCK：10.5[0.4]至 12.7[1.1]g/dL；PRINCE：11.3[1.0]至 14.0[1.3]g/dL）和接受依库珠单抗治疗但血红蛋白浓度不理想的患者（PEGASUS：10.2[0.2]至 12.8[2.6]g/dL）的平均血红蛋白浓度升高。血红蛋白浓度≥12 g/dL 的患者比例增加（PADDOCK：0 至 60.0%[3/5 例]；PRINCE：25.0%[2/8 例]至 87.5%[7/8 例]；PEGASUS：0 至 72.7%[8/11 例]）。在所有研究中，有 40.0%（2/5）（PADDOCK）、62.5%（5/8）（PRINCE）和 63.6%（7/11）（PEGASUS）的患者达到性别特异性血红蛋白正常化。平均 ARC 从高于正常水平降至正常水平，ARC 正常化增加。平均慢性疾病治疗疲劳功能评估量表评分从低于正常水平改善至接近或正常水平。2 例患者发生严重不良事件（PEGASUS：手术后脓毒症，突破性溶血）；突破性溶血在不中断研究的情况下得到解决。