Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study

被引：119

作者：

Loschi, Michael ^{[1
,2
]}

Porcher, Raphael ^{[3
]}

Barraco, Fiorenza ^{[4
]}

Terriou, Louis ^{[5
]}

Mohty, Mohamad ^{[6
]}

de Guibert, Sophie ^{[7
]}

Mahe, Beatrice ^{[8
]}

Lemal, Richard ^{[9
]}

Dumas, Pierre-Yves ^{[10
]}

Etienne, Gabriel ^{[10
]}

Jardin, Fabrice ^{[2
]}

Royer, Bruno ^{[11
]}

Bordessoule, Dominique ^{[12
]}

Rohrlich, Pierre Simon ^{[13
]}

Fornecker, Luc Mathieu ^{[14
]}

Salanoubat, Celia ^{[15
]}

Maury, Sebastien ^{[16
]}

Cahn, Jean-Yves ^{[17
]}

Vincent, Laure ^{[18
]}

Sene, Thomas ^{[19
]}

Rigaudeau, Sophie ^{[20
]}

Nguyen, Stephanie ^{[21
]}

Lepretre, Anne-Claire ^{[22
]}

Mary, Jean-Yves ^{[23
,24
]}

Corront, Bernadette ^{[25
]}

Socie, Gerard ^{[1
,24
]}

de Latour, Regis Peffault ^{[1
,24
]}

机构：

[1] St Louis Hosp, AP HP, Hematol Transplantat Dept, Paris, France

[2] Ctr Henri Becquerel, Dept Hematol, F-76038 Rouen, France

[3] Univ Paris 05, INSERM, Hop Hotel Dieu, AP HP,Ctr Clin Epidemiol,U1153, Paris, France

[4] Ctr Hosp Lyon Sud, Dept Hematol, F-69310 Pierre Benite, France

[5] Hop Claude Huriez, Dept Hematol, Lille, France

[6] St Antoine Hosp, AP HP, Dept Hematol, Paris, France

[7] Univ Hosp Pontchaillou, Dept Hematol, Rennes, France

[8] Univ Hosp, Dept Hematol, Nantes, France

[9] Univ Hosp, Dept Hematol, Clermont Ferrand, France

[10] Grp Hosp Sud, Dept Hematol, Pessac, France

[11] Univ Hosp Amiens Sud, Dept Hematol, Amiens, France

[12] Univ Hosp, Dept Hematol, Limoges, France

[13] Univ Hosp Larcher, Dept Hematol, Nice, France

[14] Univ Hosp Hautepierre, Dept Hematol, Strasbourg, France

[15] Hosp Sud Francilien, Dept Hematol, Corbeil Essonnes, France

[16] Henri Mondor Hosp, AP HP, Dept Hematol, Creteil, France

[17] Univ Hosp, Dept Hematol, Grenoble, France

[18] Univ Hosp, Dept Hematol, Montpellier, France

[19] Foch Hosp, Dept Internal Med, Paris, France

[20] Versailles Hosp, Dept Hematol, Versailles, France

[21] Hop La Pitie Salpetriere, AP HP, Dept Hematol, Paris, France

[22] Etab Francais Du Sang, Transfus Dept, Paris, France

[23] St Louis Hosp, AP HP, INSERM, U1153,Stat, Paris, France

[24] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France

[25] Annecy Hosp, Dept Hematol, Annecy, France

来源：

AMERICAN JOURNAL OF HEMATOLOGY | 2016年 / 91卷 / 04期

关键词：

COMPLEMENT INHIBITOR ECULIZUMAB; INTRAVASCULAR HEMOLYSIS; NATURAL-HISTORY; DIAGNOSIS; EFFICACY; SAFETY;

D O I：

10.1002/ajh.24278

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Intravascular hemolysis in Paroxysmal nocturnal hemoglobinuria (PNH) can effectively be controlled with eculizumab, a humanized monoclonal antibody that binds complement protein C5. We report here a retrospective comparison study between 123 patients treated with eculizumab in the recent period (>2005) and 191 historical controls (from the French registry). Overall survival (OS) at 6 years was 92% (95%CI, 87 to 98) in the eculizumab cohort versus 80% (95%CI 70 to 91) in historical controls diagnosed after 1985 (HR 0.38 [0.15 to 0.94], P=0.037). There were significantly fewer thrombotic events (TEs) in the group of patients treated with eculizumab (4% [1-10]) as compared to the historical cohort (27% [20-34]). However, we found that TEs may still occur after the initiation of eculizumab treatment and that previous TEs still have a negative impact on survival. Evolutions to myelodysplastic syndrome or acute leukemia were similar in both cohorts. There was less evolution to aplastic anemia in the treatment group. In multivariate analysis, absence of a previous TE and treatment with eculizumab were associated with a better OS. Treatment with eculizumab improves overall survival in classic PNH patients without increasing the risk of clonal evolution. Am. J. Hematol. 91:366-370, 2016. (c) 2016 Wiley Periodicals, Inc.

引用

页码：366 / 370

页数：5

共 26 条

[1] Guidelines for the Diagnosis and Monitoring of Paroxysmal Nocturnal Hemoglobinuria and Related Disorders by Flow Cytometry [J].

Borowitz, Michael J. ;

Craig, Fiona E. ;

DiGiuseppe, Joseph A. ;

Illingworth, Andrea J. ;

Rosse, Wendell ;

Sutherland, D. Robert ;

Wittwer, Carl T. ;

Richards, Stephen J. .

CYTOMETRY PART B-CLINICAL CYTOMETRY, 2010, 78B (04) :211-228

[2] Paroxysmal nocturnal hemoglobinuria:: natural history of disease subcategories [J].

de Latour, Regis Peffault ;

Mary, Jean Yves ;

Salanoubat, Celia ;

Terriou, Louis ;

Etienne, Gabriel ;

Mohty, Mohamad ;

Roth, Sophie ;

de Guibert, Sophie ;

Maury, Sebastien ;

Cahn, Jean Yves ;

Socie, Gerard .

BLOOD, 2008, 112 (08) :3099-3106

[3] Assessing complement blockade in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab [J].

de Latour, Regis Peffault ;

Fremeaux-Bacchi, Veronique ;

Porcher, Raphael ;

Xhaard, Alienor ;

Rosain, Jeremie ;

Castaneda, Diana Cadena ;

Vieira-Martins, Paula ;

Roncelin, Stephane ;

Rodriguez-Otero, Paula ;

Plessier, Aurelie ;

de Fontbrune, Flore Sicre ;

Abbes, Sarah ;

Robin, Marie ;

Socie, Gerard .

BLOOD, 2015, 125 (05) :775-783

[4] Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria [J].

de Latour, Regis Peffault ;

Schrezenmeier, Hubert ;

Bacigalupo, Andrea ;

Blaise, Didier ;

de Souza, Carmino A. ;

Vigouroux, Stephane ;

Willemze, Roelf ;

Terriou, Louis ;

Tichelli, Andre ;

Mohty, Mohamad ;

de Guibert, Sophie ;

Marsh, Judith C. ;

Passweg, Jakob ;

Mary, Jean Yves ;

Socie, Gerard .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2012, 97 (11) :1666-1673

[5] Th17 immune responses contribute to the pathophysiology of aplastic anemia [J].

de Latour, Regis Peffault ;

Visconte, Valeria ;

Takaku, Tomoiku ;

Wu, Colin ;

Erie, Andrew J. ;

Sarcon, Annahita K. ;

Desierto, Marie J. ;

Scheinberg, Phillip ;

Keyvanfar, Keyvan ;

Nunez, Olga ;

Chen, Jichun ;

Young, Neal S. .

BLOOD, 2010, 116 (20) :4175-4184

[6] The use of monoclonal antibodies and flow cytometry in the diagnosis of paroxysmal nocturnal hemoglobinuria [J].

Hall, SE ;

Rosse, WF .

BLOOD, 1996, 87 (12) :5332-5340

[7] Thrombosis in paroxysmal nocturnal hemoglobinuria [J].

Hill, Anita ;

Kelly, Richard J. ;

Hillmen, Peter .

BLOOD, 2013, 121 (25) :4985-4996

[8] Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization [J].

Hill, Anita ;

Rother, Russell P. ;

Arnold, Louise ;

Kelly, Richard ;

Cullen, Matthew J. ;

Richards, Stephen J. ;

Hillmen, Peter .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2010, 95 (04) :567-573

[9] Effect of eculizumab on haemolysis-associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria [J].

Hill, Anita ;

Rother, Russell P. ;

Wang, Xunde ;

Morris, Sidney M., Jr. ;

Quinn-Senger, Kerry ;

Kelly, Richard ;

Richards, Stephen J. ;

Bessler, Monica ;

Bell, Leonard ;

Hillmen, Peter ;

Gladwin, Mark T. .

BRITISH JOURNAL OF HAEMATOLOGY, 2010, 149 (03) :414-425

[10] NATURAL-HISTORY OF PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA [J].

HILLMEN, P ;

LEWIS, SM ;

BESSLER, M ;

LUZZATTO, L ;

DACIE, JV .

NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (19) :1253-1258

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