Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria
- Author(s)
- Peffault de Latour, R; Griffin, M; Kelly, RJ; Szer, J; de Castro, C; Horneff, R; Tan, L; Yeh, M; Panse, J;
- Details
- Publication Year 2024-06-11,Volume 8,Issue #11,Page 2718-2725
- Journal Title
- Blood Advances
- Publication Type
- Research article
- Abstract
- Patients with paroxysmal nocturnal hemoglobinuria (PNH) experience complement-mediated intravascular hemolysis leading to anemia, fatigue, and potentially life-threatening thrombotic complications. Pegcetacoplan, a C3 inhibitor, demonstrated sustained improvements in hematologic and clinical parameters in the phase 3 PEGASUS trial in patients with PNH who remained anemic despite C5 inhibitor therapy. The present post hoc analysis describes 26 hemolysis adverse events (AEs) experienced in 19 patients during pegcetacoplan therapy in PEGASUS and baseline patient characteristics potentially associated with increased hemolysis risk. Lactate dehydrogenase (LDH) ≥2× the upper limit of normal (ULN) was observed in 19 events, including 2 with LDH ≥10× ULN. All patients experienced decreased hemoglobin during hemolysis (mean decrease, 3.0 g/dL). In 16 events (62%), a potential complement-amplifying condition underlying the event could be identified. Hemolysis AEs led to study discontinuation in 5 patients. However, of 26 hemolysis AEs, 17 (65%) were manageable without pegcetacoplan discontinuation. A greater proportion of patients with hemolysis AEs (n = 19) had key characteristics of higher disease activity at baseline compared to patients without hemolysis AEs (n = 61), namely higher-than-label eculizumab dose (53% vs 23%), detectable CH50 (total complement function; 74% vs 54%), and ≥4 transfusions in the previous 12 months (68% vs 51%). These characteristics may be useful predictors of potential future hemolysis events. This trial was registered at www.ClinicalTrials.gov as #NCT03500549.
- Publisher
- American Society of Hematology
- Keywords
- Humans; *Hemoglobinuria, Paroxysmal/drug therapy/complications; *Hemolysis; Male; Female; Middle Aged; *Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects; Adult; Aged; Complement C3/metabolism; Complement Inactivating Agents/therapeutic use
- Department(s)
- Clinical Haematology
- Publisher's Version
- https://doi.org/10.1182/bloodadvances.2024012672
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-07-17 04:32:35
Last Modified: 2024-07-17 04:35:46