Title :

Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study.

Author(s) :

Guillet, Stéphanie [Auteur]
Hôpital Henri Mondor
Crickx, Etienne [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
CHU Henri Mondor [Créteil]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Azzaoui, Imane [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
CHU Henri Mondor [Créteil]
Chappert, Pascal [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Boutin, Emmanuelle [Auteur]
Hôpital Henri Mondor
IMRB - CEPIA/"Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health" [Créteil] [U955 Inserm - UPEC]
Viallard, Jean-François [Auteur]
Hôpital Haut-Lévêque [CHU Bordeaux]
Riviere, Etienne [Auteur]
Hôpital Haut-Lévêque [CHU Bordeaux]
Gobert, Delphine [Auteur]
CHU Saint-Antoine [AP-HP]
Galicier, Lionel [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Malphettes, Marion [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Cheze, Stéphane [Auteur]
CHU Caen
Lefrere, François [Auteur]
Département de Biothérapie [CHU Necker]
Audia, Sylvain [Auteur]
Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand [CHU Dijon]
Bonnotte, Bernard [Auteur]
Centre de référence des maladies rares des cytopénies auto-immunes de l'adulte (CHU Dijon) [CRMR des cytopénies auto-immunes de l'adulte ]
Lambotte, Olivier [Auteur]

Noel, Nicolas [Auteur]

Fain, Olivier [Auteur]
CHU Saint-Antoine [AP-HP]
Moulis, Guillaume [Auteur]
Centre Hospitalier Universitaire de Toulouse [CHU Toulouse]
Hamidou, Mohamed [Auteur]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Gerfaud-Valentin, Mathieu [Auteur]
Hôpital de la Croix-Rousse [CHU - HCL]
Marolleau, Jean-Pierre [Auteur]
CHU Amiens-Picardie
Terriou, Louis [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Martis, Nihal [Auteur]
Centre Hospitalier Universitaire de Nice [CHU Nice]
Morin, Anne-Sophie [Auteur]
Hôpital Jean Verdier [AP-HP]
Perlat, Antoinette [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
Le Gallou, Thomas [Auteur]
Centre Hospitalier Universitaire [Rennes]
Roy-Peaud, Frédérique [Auteur]
Centre hospitalier universitaire de Poitiers = Poitiers University Hospital [CHU de Poitiers [La Milétrie]]
Robbins, Ailsa [Auteur]
Hôpital universitaire Robert Debré [Reims] [CHU Reims]
Lega, Jean-Christophe [Auteur]
Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
Puyade, Matthieu [Auteur]
Centre hospitalier universitaire de Poitiers = Poitiers University Hospital [CHU de Poitiers [La Milétrie]]
Comont, Thibault [Auteur]
Centre Hospitalier Universitaire de Toulouse [CHU Toulouse]
Limal, Nicolas [Auteur]
Hôpital Henri Mondor
Languille, Laetitia [Auteur]
Hôpital Henri Mondor
Zarour, Anissa [Auteur]
Hôpital Henri Mondor
Luka, Marine [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Ménager, Mickael [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Belmondo, Thibault [Auteur]
Hôpital Henri Mondor
Hue, Sophie [Auteur]
Hôpital Henri Mondor
Canoui-Poitrine, Florence [Auteur]
Hôpital Henri Mondor
Michel, Marc [Auteur]
Centre de référence des maladies rares des cytopénies auto-immunes de l'adulte (CHU Dijon) [CRMR des cytopénies auto-immunes de l'adulte ]
Godeau, Bertrand [Auteur]
Centre de référence des maladies rares des cytopénies auto-immunes de l'adulte (CHU Dijon) [CRMR des cytopénies auto-immunes de l'adulte ]
Mahevas, Matthieu [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Centre de référence des maladies rares des cytopénies auto-immunes de l'adulte (CHU Dijon) [CRMR des cytopénies auto-immunes de l'adulte ]

Journal title :

Blood

Abbreviated title :

Blood

Publication date :

2023-03-11

ISSN :

1528-0020

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic ...
Show more >Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response on TPO-RAs. The primary endpoint was the proportion of patients achieving SROT (platelet count > 30x109/L and no bleeding) at W24 with no other ITP-specific medications. Secondary endpoints included the proportion of sustained complete response off-treatment (SCROT, platelet count > 100x109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with median (IQR) age 58.5 years (41-73.5); 30/48 (63%) had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27/48 (56.2%, 95% CI, 41.2-70.5) achieved SROT; 15/48 (31.3%; 95% CI, 18.9-44.5) achieved SCROT at W24, and 25/48 (52.1%; 95% CI, 37.2-66.7) achieved respectively SROT and 14/48 (29.2%; 95% CI, 17.2-42.3) SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients re-challenged with TPO-RA, 11/12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA-seq revealed enrichment of a "TNFα signaling via NF-κB" signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based of progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. Clinical trial number: NCT03119974Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-01-11T23:11:58Z
2024-03-07T09:49:02Z