Northwestern University, Chicago, IL, USA.
Apellis Pharmaceuticals, Inc., Waltham, MA, USA.
Ann Hematol. 2022 Sep;101(9):1905-1914. doi: 10.1007/s00277-022-04887-8. Epub 2022 Jul 23.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, acquired, hematologic, life-threatening disease characterized by thrombosis, impaired bone marrow function, and complement-mediated hemolysis. The PEGASUS phase III clinical trial demonstrated superiority of pegcetacoplan over eculizumab regarding improvements in hemoglobin levels in patients with suboptimal response to prior eculizumab treatment. The objective of this post hoc analysis was to compare the patient-reported outcome (PRO) response rates observed among PEGASUS participants and the relationships between their PRO scores with clinical and hematological parameters. Data from the 16-week randomized, controlled (1:1 to pegcetacoplan or eculizumab) period of the PEGASUS trial included comparisons of weekly PRO measurements taken using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) scales. A clinically meaningful FACIT-F response was defined as an increase from baseline of ≥5 points. Convergent validity was assessed using conventional threshold correlations between FACIT-F, EORTC QLQ-C30, and laboratory parameters. A clinically meaningful improvement in FACIT-F score was seen in 72.2% of pegcetacoplan-treated patients compared to 22.9% of eculizumab-treated patients. At week 16, the FACIT-F total score correlated with hemoglobin levels (r=0.47, p< 0.0001), absolute reticulocyte count (r=-0.37, p<0.01), and indirect bilirubin levels (r=-0.25, p<0.05). Clinically meaningful improvements in pegcetacoplan-treated patients were also observed for multiple EORTC scales. Fatigue and other self-reported outcomes were correlated with clinically meaningful improvements in clinical and hematological parameters. Clinical trial registration: NCT03500549.
阵发性睡眠性血红蛋白尿症 (PNH) 是一种罕见的、慢性的、获得性的血液学疾病，以血栓形成、骨髓功能受损和补体介导的溶血为特征。PEGASUS 三期临床试验表明，在对既往依库珠单抗治疗反应不佳的患者中，培戈洛珠单抗在血红蛋白水平改善方面优于依库珠单抗。本次事后分析的目的是比较 PEGASUS 参与者中观察到的患者报告结局 (PRO) 反应率，以及他们的 PRO 评分与临床和血液学参数之间的关系。PEGASUS 试验的 16 周随机、对照（1:1 至培戈洛珠单抗或依库珠单抗）期间的数据包括使用慢性病治疗功能评估-疲劳量表 (FACIT-F) 和欧洲癌症研究和治疗组织生活质量问卷核心 30 量表 (EORTC QLQ-C30) 每周进行的 PRO 测量的比较。临床有意义的 FACIT-F 反应定义为与基线相比增加≥5 分。采用 FACIT-F、EORTC QLQ-C30 和实验室参数之间的传统阈值相关性评估趋同效度。与依库珠单抗治疗组的 22.9%相比，培戈洛珠单抗治疗组有 72.2%的患者出现 FACIT-F 评分的临床显著改善。在第 16 周时，FACIT-F 总分与血红蛋白水平（r=0.47，p<0.0001）、绝对网织红细胞计数（r=-0.37，p<0.01）和间接胆红素水平（r=-0.25，p<0.05）相关。在培戈洛珠单抗治疗组中，还观察到对多个 EORTC 量表的临床有意义的改善。疲劳和其他自我报告的结局与临床和血液学参数的临床意义改善相关。临床试验注册：NCT03500549。
