Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry

Hubert Schrezenmeier; Alexander Röth; David J. Araten; Yuzuru Kanakura; Loree Larratt; Jamile M. Shammo; Amanda Wilson; Gilda Shayan; Jaroslaw P. Maciejewski

doi:10.1007/s00277-020-04052-z

Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry

Hubert Schrezenmeier^*, Alexander Röth, David J. Araten, Yuzuru Kanakura, Loree Larratt, Jamile M. Shammo, Amanda Wilson, Gilda Shayan, Jaroslaw P. Maciejewski

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

Abstract

The International Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry (NCT01374360) was initiated to optimize patient management by collecting data regarding disease burden, progression, and clinical outcomes. Herein, we report updated baseline demographics, clinical characteristics, disease burden data, and observed trends regarding clone size in the largest cohort of Registry patients. Patients with available data as of July 2017 were stratified by glycosylphosphatidylinositol (GPI)-deficient granulocyte clone size (< 10%, ≥ 10%–< 50%, and ≥ 50%). All patients were untreated with eculizumab at baseline, defined as date of eculizumab initiation or date of Registry enrollment (if never treated with eculizumab). Outcomes assessed in the current analysis included proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVEs; including thrombotic events [TEs]), bone marrow failure (BMF), red blood cell (RBC) transfusions, and PNH-related symptoms. A total of 4439 patients were included, of whom 2701 (60.8%) had available GPI-deficient granulocyte clone size data. Among these, median clone size was 31.8% (1002 had < 10%; 526 had ≥ 10%–< 50%; 1173 had ≥ 50%). There were high proportions of patients with HDA (51.6%), history of MAVEs (18.8%), BMF (62.6%), RBC transfusion (61.3%), and impaired renal function (42.8%). All measures except RBC transfusion history significantly correlated with GPI-deficient granulocyte clone size. A large proportion of patients with GPI-deficient granulocyte clone size < 10% had hemolysis (9.7%), MAVEs (10.2%), HDA (9.1%), and/or PNH-related symptoms. Although larger GPI-deficient granulocyte clone sizes were associated with higher disease burden, a substantial proportion of patients with smaller clone sizes had history of MAVEs/TEs.

Original language	English (US)
Pages (from-to)	1505-1514
Number of pages	10
Journal	Annals of Hematology
Volume	99
Issue number	7
DOIs	https://doi.org/10.1007/s00277-020-04052-z
State	Published - Jul 1 2020

Funding

Open Access funding provided by Projekt DEAL. This study was funded by Alexion Pharmaceuticals, Inc. Acknowledgments Data availability statement This analysis was sponsored by Alexion Pharmaceuticals, Inc., Boston, MA, USA. Alexion provided a scientific accuracy review of their data. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit. The sponsor had no influence on the interpretation of the data or reporting of the results. The decision to submit the manuscript was made independently by the authors with no influence from the sponsor. The sponsor and investigators thank the patients and their families for their participation in and support for this clinical study. The authors would like to acknowledge Peloton Advantage, LLC, an OPEN Health company, which provided editorial and medical writing support by Michael D. Morren, RPh, MBA, with funding from Alexion Pharmaceuticals, Inc., and Kirsten Zu, ScD, PhD, of Alexion Pharmaceuticals, Inc., for additional statistical analysis support. Hubert Schrezenmeier has received honoraria and research support (both to University of Ulm) from Alexion Pharmaceuticals, Inc., and honoraria (to University of Ulm) from Ra Pharma, Roche, and Alnylam Pharmaceuticals. Alexander Röth has received honoraria and consulting fees from Alexion Pharmaceuticals, Inc., Roche, and Novartis, and research support from Alexion Pharmaceuticals, Inc., and Roche. David J. Araten has received honoraria and consulting fees from Alexion Pharmaceuticals, Inc. Yuzuru Kanakura has received honoraria and research support from Alexion Pharmaceuticals, Inc. Loree Larratt has received honoraria and research support (for the laboratory at the University of Alberta, for ADAMTS13 testing) from Alexion Pharmaceuticals, Inc. Jamile M. Shammo has received honoraria, consulting fees, and research support from Alexion Pharmaceuticals, Inc. Amanda Wilson and Gilda Shayan are former employees and stockholders of Alexion Pharmaceuticals, Inc. Jaroslaw P. Maciejewski has received consulting fees from Alexion Pharmaceuticals, Inc., Apellis Pharmaceuticals, and Ra Pharma; has also received speaker fees from Alexion Pharmaceuticals, Inc. and is a member of the Executive Committee of International PNH Registry for Alexion Pharmaceuticals, Inc.

Keywords

Bone marrow failure
Eculizumab
Health-related quality of life
Paroxysmal nocturnal hemoglobinuria
Registries
Thrombosis

ASJC Scopus subject areas

Hematology

Access to Document

10.1007/s00277-020-04052-z

Cite this

Schrezenmeier, H., Röth, A., Araten, D. J., Kanakura, Y., Larratt, L., Shammo, J. M., Wilson, A., Shayan, G., & Maciejewski, J. P. (2020). Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry. Annals of Hematology, 99(7), 1505-1514. https://doi.org/10.1007/s00277-020-04052-z

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Schrezenmeier, H, Röth, A, Araten, DJ, Kanakura, Y, Larratt, L, Shammo, JM, Wilson, A, Shayan, G & Maciejewski, JP 2020, 'Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry', Annals of Hematology, vol. 99, no. 7, pp. 1505-1514. https://doi.org/10.1007/s00277-020-04052-z

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AU - Schrezenmeier, Hubert

AU - Röth, Alexander

AU - Araten, David J.

AU - Kanakura, Yuzuru

AU - Larratt, Loree

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AU - Wilson, Amanda

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AU - Maciejewski, Jaroslaw P.

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N2 - The International Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry (NCT01374360) was initiated to optimize patient management by collecting data regarding disease burden, progression, and clinical outcomes. Herein, we report updated baseline demographics, clinical characteristics, disease burden data, and observed trends regarding clone size in the largest cohort of Registry patients. Patients with available data as of July 2017 were stratified by glycosylphosphatidylinositol (GPI)-deficient granulocyte clone size (< 10%, ≥ 10%–< 50%, and ≥ 50%). All patients were untreated with eculizumab at baseline, defined as date of eculizumab initiation or date of Registry enrollment (if never treated with eculizumab). Outcomes assessed in the current analysis included proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVEs; including thrombotic events [TEs]), bone marrow failure (BMF), red blood cell (RBC) transfusions, and PNH-related symptoms. A total of 4439 patients were included, of whom 2701 (60.8%) had available GPI-deficient granulocyte clone size data. Among these, median clone size was 31.8% (1002 had < 10%; 526 had ≥ 10%–< 50%; 1173 had ≥ 50%). There were high proportions of patients with HDA (51.6%), history of MAVEs (18.8%), BMF (62.6%), RBC transfusion (61.3%), and impaired renal function (42.8%). All measures except RBC transfusion history significantly correlated with GPI-deficient granulocyte clone size. A large proportion of patients with GPI-deficient granulocyte clone size < 10% had hemolysis (9.7%), MAVEs (10.2%), HDA (9.1%), and/or PNH-related symptoms. Although larger GPI-deficient granulocyte clone sizes were associated with higher disease burden, a substantial proportion of patients with smaller clone sizes had history of MAVEs/TEs.

AB - The International Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry (NCT01374360) was initiated to optimize patient management by collecting data regarding disease burden, progression, and clinical outcomes. Herein, we report updated baseline demographics, clinical characteristics, disease burden data, and observed trends regarding clone size in the largest cohort of Registry patients. Patients with available data as of July 2017 were stratified by glycosylphosphatidylinositol (GPI)-deficient granulocyte clone size (< 10%, ≥ 10%–< 50%, and ≥ 50%). All patients were untreated with eculizumab at baseline, defined as date of eculizumab initiation or date of Registry enrollment (if never treated with eculizumab). Outcomes assessed in the current analysis included proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVEs; including thrombotic events [TEs]), bone marrow failure (BMF), red blood cell (RBC) transfusions, and PNH-related symptoms. A total of 4439 patients were included, of whom 2701 (60.8%) had available GPI-deficient granulocyte clone size data. Among these, median clone size was 31.8% (1002 had < 10%; 526 had ≥ 10%–< 50%; 1173 had ≥ 50%). There were high proportions of patients with HDA (51.6%), history of MAVEs (18.8%), BMF (62.6%), RBC transfusion (61.3%), and impaired renal function (42.8%). All measures except RBC transfusion history significantly correlated with GPI-deficient granulocyte clone size. A large proportion of patients with GPI-deficient granulocyte clone size < 10% had hemolysis (9.7%), MAVEs (10.2%), HDA (9.1%), and/or PNH-related symptoms. Although larger GPI-deficient granulocyte clone sizes were associated with higher disease burden, a substantial proportion of patients with smaller clone sizes had history of MAVEs/TEs.

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Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry

Abstract

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