Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study
Louis Loschi
(1, 2)
,
Raphaël Porcher
(3, 4, 5)
,
Fiorenza Barraco
(6)
,
Louis Terriou
(7)
,
Mohamad Mohty
(8)
,
Sophie de Guibert
(9)
,
Beatrice Mahe
(10)
,
Richard Lemal
(11)
,
Pierre-Yves Dumas
(12)
,
Gabriel Etienne
(12)
,
Fabrice Jardin
(2)
,
Bruno Royer
(13)
,
Dominique Bordessoule
(14)
,
Pierre Simon Rohrlich
(15)
,
Luc Mathieu Fornecker
(16)
,
Celia Salanoubat
(17)
,
Sébastien Maury
(18)
,
Jean-Yves Cahn
(19)
,
Laure Vincent
(20, 21)
,
Thomas Sené
(22)
,
Sophie Rigaudeau
(23)
,
Stephanie Nguyen
(24)
,
Anne-Claire Lepretre
(25)
,
Jean-Yves Mary
(1, 26)
,
Bernadette Corront
(27)
,
Gérard Socié
(28, 26)
,
Régis Peffault de Latour
(29, 26)
1
AP-HP -
Hopital Saint-Louis [AP-HP]
2 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
3 CRESS (U1153 / UMR_A_1125 / UMR_S_1153) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité
4 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
5 UPD5 - Université Paris Descartes - Paris 5
6 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
7 Hôpital Claude Huriez [Lille]
8 CHU Saint-Antoine [AP-HP]
9 Service d'hématologie clinique
10 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
11 CHELTER - Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias
12 GHSIF - Groupe Hospitalier Sud Ile-de-France
13 CHU Amiens-Picardie
14 CHU Limoges
15 CHU - Hôpital Archet 2 [Nice]
16 Hôpital de Hautepierre [Strasbourg]
17 Centre Hospitalier Sud Francilien
18 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
19 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
20 UM - Université de Montpellier
21 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
22 Hôpital Foch [Suresnes]
23 CHV - Centre Hospitalier de Versailles André Mignot
24 CHU Pitié-Salpêtrière [AP-HP]
25 EFS - Etablissement Français du Sang [La Plaine Saint-Denis]
26 UPD7 - Université Paris Diderot - Paris 7
27 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
28 Service de greffe de moelle osseuse [Saint-Louis]
29 IUH - Institut Universitaire d'Hématologie
2 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
3 CRESS (U1153 / UMR_A_1125 / UMR_S_1153) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité
4 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
5 UPD5 - Université Paris Descartes - Paris 5
6 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
7 Hôpital Claude Huriez [Lille]
8 CHU Saint-Antoine [AP-HP]
9 Service d'hématologie clinique
10 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
11 CHELTER - Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias
12 GHSIF - Groupe Hospitalier Sud Ile-de-France
13 CHU Amiens-Picardie
14 CHU Limoges
15 CHU - Hôpital Archet 2 [Nice]
16 Hôpital de Hautepierre [Strasbourg]
17 Centre Hospitalier Sud Francilien
18 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
19 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
20 UM - Université de Montpellier
21 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
22 Hôpital Foch [Suresnes]
23 CHV - Centre Hospitalier de Versailles André Mignot
24 CHU Pitié-Salpêtrière [AP-HP]
25 EFS - Etablissement Français du Sang [La Plaine Saint-Denis]
26 UPD7 - Université Paris Diderot - Paris 7
27 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
28 Service de greffe de moelle osseuse [Saint-Louis]
29 IUH - Institut Universitaire d'Hématologie
Raphaël Porcher
- Fonction : Auteur
- PersonId : 756384
- ORCID : 0000-0002-5277-4679
- IdRef : 071086757
Gabriel Etienne
- Fonction : Auteur
- PersonId : 756576
- ORCID : 0000-0001-7600-4954
Stephanie Nguyen
- Fonction : Auteur
- PersonId : 752190
- IdHAL : nguyen-stephanie
Gérard Socié
- Fonction : Auteur
- PersonId : 758626
- ORCID : 0000-0002-2114-7533
- IdRef : 061658243
Régis Peffault de Latour
- Fonction : Auteur
- PersonId : 762864
- ORCID : 0000-0001-6222-4753
- IdRef : 092887112
Résumé
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.