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• W4294335448 abstract "Letter to Blood| January 5, 2023 Experience of compassionate-use pegcetacoplan for paroxysmal nocturnal hemoglobinuria Clinical Trials & Observations Morag Griffin, Morag Griffin 1Haematology Department, St James University Hospital, Leeds, United Kingdom https://orcid.org/0000-0002-4287-0595 Search for other works by this author on: This Site PubMed Google Scholar Petra Muus, Petra Muus 1Haematology Department, St James University Hospital, Leeds, United Kingdom https://orcid.org/0000-0002-2560-3882 Search for other works by this author on: This Site PubMed Google Scholar Talha Munir, Talha Munir 1Haematology Department, St James University Hospital, Leeds, United Kingdom Search for other works by this author on: This Site PubMed Google Scholar Sateesh Nagumantry, Sateesh Nagumantry 2Haematology Department, Peterborough Hospital, North West Anglia NHS Foundation Trust, Peterborough, United Kingdom Search for other works by this author on: This Site PubMed Google Scholar Alexandra Pike, Alexandra Pike 1Haematology Department, St James University Hospital, Leeds, United Kingdom https://orcid.org/0000-0002-6115-421X Search for other works by this author on: This Site PubMed Google Scholar Louise Arnold, Louise Arnold 1Haematology Department, St James University Hospital, Leeds, United Kingdom Search for other works by this author on: This Site PubMed Google Scholar Briony Forrest, Briony Forrest 1Haematology Department, St James University Hospital, Leeds, United Kingdom Search for other works by this author on: This Site PubMed Google Scholar Catherine Barnfield, Catherine Barnfield 1Haematology Department, St James University Hospital, Leeds, United Kingdom Search for other works by this author on: This Site PubMed Google Scholar Nicola Houghton, Nicola Houghton 1Haematology Department, St James University Hospital, Leeds, United Kingdom Search for other works by this author on: This Site PubMed Google Scholar Nora Youngs, Nora Youngs 1Haematology Department, St James University Hospital, Leeds, United Kingdom Search for other works by this author on: This Site PubMed Google Scholar Richard Kelly Richard Kelly 1Haematology Department, St James University Hospital, Leeds, United Kingdom Search for other works by this author on: This Site PubMed Google Scholar Blood (2023) 141 (1): 116–120. https://doi.org/10.1182/blood.2022017266 Article history Submitted: May 31, 2022 Accepted: August 12, 2022 Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Morag Griffin, Petra Muus, Talha Munir, Sateesh Nagumantry, Alexandra Pike, Louise Arnold, Briony Forrest, Catherine Barnfield, Nicola Houghton, Nora Youngs, Richard Kelly; Experience of compassionate-use pegcetacoplan for paroxysmal nocturnal hemoglobinuria. Blood 2023; 141 (1): 116–120. doi: https://doi.org/10.1182/blood.2022017266 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Clinical Trials and Observations, Red Cells, Iron, and Erythropoiesis TO THE EDITOR: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired condition characterized by intravascular hemolysis (IVH) and thrombosis. Patients classically have elevated levels of lactate dehydrogenase (LDH) and anemia.1,2 Eculizumab has significantly improved life expectancy.3 Eculizumab and ravulizumab bind at complement protein C5 in the complement cascade, inhibiting terminal complement activation, preventing IVH, and reducing thrombosis risk.4,5 Two-thirds of the patients on C5 inhibition are anemic due to C3 red cell opsonization, leading to extravascular hemolysis (EVH), and one-third require blood transfusions.6-8 EVH is often represented by a disproportionally low percentage of PNH erythrocytes compared with PNH white cells and high PNH red cell C3 loading. Pegcetacoplan, which targets proximal complement protein C3, prevents IVH and EVH. The PEGASUS clinical trial for patients with PNH on eculizumab with hemoglobin (Hb) of <105... References 1.Hillmen P, Lewis S, Bessler M, Luzzatto L, Dacie J. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333(19):1253-1258.Google ScholarCrossrefSearch ADS 2.Socié G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet. 1996;348(9027):573-577.Google ScholarCrossrefSearch ADS PubMed 3.Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011;117(25):6786-6792.Google ScholarCrossrefSearch ADS PubMed 4.Hillmen P, Muus P, Dührsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007;110(12):4123-4128.Google ScholarCrossrefSearch ADS PubMed 5.Kulasekararaj AG, Hill A, Langemeijer S, et al. One-year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab. Eur J Haematol. 2021;106(3):389-397.Google ScholarCrossrefSearch ADS PubMed 6.McKinley CE, Richards S, Munir T, et al. Extravascular hemolysis due to C3-loading in patients with PNH treated with eculizumab: defining the clinical syndrome [abstract]. Blood. 2017;130(suppl 1).Google Scholar 7.Risitano AM, Notaro R, Marando L, et al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 2009;113(17):4094-4100.Google ScholarCrossrefSearch ADS PubMed 8.Sica M, Rondelli T, Ricci P, Angioletti M, Risitano A, Notaro R. Eculizumab treatment: stochastic occurrence of C3 binding to individual PNH erythrocytes. J Hematol Oncol. 2017;10(126):1-10.Google Scholar 9.Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2021;384(11):1028-1037.Google ScholarCrossrefSearch ADS 10.Brodsky RA, Peffault de Latour R, Rottinghaus ST, et al. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Hematologica. 2021;106(1):230-237.Google ScholarCrossrefSearch ADS 11.Risitano A, Marotta S, Ricci P, et al. Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019;10(1157):1-24.Google ScholarPubMed 12.Kelly R, Arnold L, Richards S, et al. Modification of the eculizumab dose to successfully manage intravascular breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria [abstract]. Blood. 2008;112(11).Google Scholar 13.Notaro R, Luzzatto L. Breakthrough hemolysis in PNH with proximal and terminal complement inhibition. N Engl J Med. 2022;387(2):160-166.Google ScholarCrossrefSearch ADS 14.de Latour R, Szer J, Weitz I, et al. Forty eight week efficacy and safety of Pegcetacoplan in adult patients with paroxysmal nocturnal hemoglobinuria and suboptimal response to prior eculizumab treatment. EHA Library; 2021:324582. © 2023 by The American Society of Hematology2023 © 2023 by The American Society of Hematology2023 You do not currently have access to this content. Sign in via your Institution" @default.
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