Roman Eloy, Fattizzo Bruno, Shum Merrill, Hanna Wahid, Lentz Steven R, Araujo Sergio Schusterschitz S, Al-Adhami Mohammed, Grossi Federico V, Gertz Morie A
Hematology-Oncology, Lakes Research, Miami Lakes, FL.
Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Blood. 2025 Jan 23;145(4):397-408. doi: 10.1182/blood.2023022549.
Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, largely attributable to complement activation resulting in intravascular and extravascular hemolysis. Pegcetacoplan is a subcutaneously administered C3-targeted therapy, which may be suitable for treating CAD and wAIHA. In this open-label phase 2 study, analyses were conducted in 2 cohorts, 1 for patients with CAD and the other for those with wAIHA. In each cohort, patients were randomly assigned to receive pegcetacoplan 270 mg/d or 360 mg/d for up to 48 weeks. Safety end points included the incidence and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Efficacy end points included change from baseline in hemoglobin (Hb), lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and functional assessment of chronic illness therapy (FACIT)-fatigue scale. Thirteen of 13 (100%) and 10 of 11 (91%) patients with CAD and wAIHA, respectively, experienced at least 1 TEAE. Ten patients had at least 1 serious AE; none were considered related to pegcetacoplan. The only treatment-related AESIs were injection site reactions. Pegcetacoplan increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in the first weeks; at week 48 the median (interquartile range) change from baseline Hb for the CAD and wAIHA total groups was 2.4 (0.90-3.00) and 1.7 g/dL (-1.40 to 2.90), respectively, and improvements in hemolysis and FACIT-fatigue scale scores were maintained. This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective for patients with CAD and wAIHA. This trial was registered at www.ClinicalTrials.gov as #NCT03226678.
冷凝集素病（CAD）和温抗体自身免疫性溶血性贫血（wAIHA）是罕见的自身免疫性溶血性贫血，其特征是红细胞破坏，主要归因于补体激活导致血管内和血管外溶血。培格西他单抗是一种皮下注射的靶向C3疗法，可能适用于治疗CAD和wAIHA。在这项开放标签的2期研究中，对2个队列进行了分析，1个队列是CAD患者，另1个队列是wAIHA患者。在每个队列中，患者被随机分配接受270mg/d或360mg/d的培格西他单抗治疗，最长治疗48周。安全性终点包括治疗期间出现的不良事件（TEAE）和特殊关注不良事件（AESI）的发生率和严重程度。疗效终点包括血红蛋白（Hb）、乳酸脱氢酶、绝对网织红细胞计数、触珠蛋白、间接胆红素从基线的变化以及慢性病治疗功能评估（FACIT）-疲劳量表。CAD患者中的13例（100%）和wAIHA患者中的10例（91%）分别经历了至少1次TEAE。10例患者发生了至少1次严重不良事件；均不认为与培格西他单抗有关。唯一与治疗相关的AESI是注射部位反应。在最初几周内，培格西他单抗提高了Hb水平，减少了溶血，并提高了FACIT-疲劳量表评分；在第48周时，CAD和wAIHA总组从基线Hb的中位数（四分位间距）变化分别为2.4（0.90-3.00）和1.7g/dL（-1.40至2.90），溶血和FACIT-疲劳量表评分的改善得以维持。这项研究表明培格西他单抗总体耐受性良好，并表明它对CAD和wAIHA患者可能有效。该试验已在www.ClinicalTrials.gov上注册，编号为#NCT03226678。
