Real-world use of defibrotide for veno-occlusive disease/sinusoidal obstruction syndrome: the DEFIFrance Registry Study

Mohamad Mohty (1, 2) , Didier Blaise (3, 4) , Régis Peffault de Latour (1) , Myriam Labopin (1) , Jean Henri Bourhis (5) , Benedicte Bruno (6) , Patrice Ceballos (7) , Marie Detrait (8) , Virginie Gandemer (9) , Anne Huynh (10) , Faezeh Izadifar-Legrand (4) , Charlotte Jubert (11) , Hélène Labussière-Wallet (12) , Delphine Lebon (13, 14) , Sébastien Maury (15, 16) , Catherine Paillard (17) , Cécile Pochon (18) , Cecile Renard (19) , Fanny Rialland (20) , Pascale Schneider (21, 22) , Anne Sirvent (23) , Kobby Asubonteng (24) , Gwennaëlle Guindeuil (25) , Ibrahim Yakoub-Agha (26) , Jean-Hugues Dalle (27)

1 CHU Saint-Antoine [AP-HP]
2 CRSA - Centre de Recherche Saint-Antoine
3 CRCM - Centre de Recherche en Cancérologie de Marseille
4 IPC - Institut Paoli-Calmettes
5 Département d'hématologie [Gustave Roussy]
6 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
7 CHU - Hôpital Lapeyronie [Montpellier]
8 Service d'Hématologie [CHRU Nancy]
9 IGDR - Institut de Génétique et Développement de Rennes
10 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
11 Groupe hospitalier Pellegrin
12 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
13 CHU Amiens-Picardie
14 HEMATIM - HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666
15 UPEC Médecine - Université Paris-Est Créteil Val-de-Marne - Faculté de médecine
16 Hôpital Henri Mondor
17 CIC 1405 - Centre d'Investigation Clinique [CHU Clermont-Ferrand]
18 Service d'Oncologie Pédiatrique [CHRU Nancy]
19 Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL]
20 CHU Nantes - Centre Hospitalier Universitaire de Nantes
21 Service de pédiatrie médicale et médecine de l'adolescent [Rouen]
22 PANTHER - Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices
23 CHU Montpellier
24 Jazz Pharmaceuticals, Inc
25 Jazz Pharmaceuticals [Lyon]
26 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
27 Hôpital Robert Debré Paris

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic cell transplantation (HCT) conditioning. The DEFIFrance post-marketing registry study evaluated effectiveness and safety in patients who received defibrotide. It collected retrospective/prospective patient data from 53 French HCT centres from July 2014 to March 2020. Primary endpoints were survival and complete response (CR; total serum bilirubin <2 mg/dL, multiorgan failure resolution) at Day 100 post-HCT among patients with severe/very severe VOD/SOS. A secondary endpoint was evaluation of treatment-emergent serious adverse events (TESAEs) of interest. Of 798 patients analysed, 251 and 81 received defibrotide treatment for severe/very severe VOD/SOS and mild/moderate VOD/SOS post-HCT, respectively; 381 received defibrotide for VOD/SOS prophylaxis. In patients with severe/very severe VOD/SOS post-HCT, Kaplan-Meier-estimated CR at Day 100 was 74% (95% confidence interval [CI]: 66%, 81%). At Day 100, 137/251 (55%) were alive and in CR. Kaplan-Meier-estimated Day 100 post-HCT survival was 61% (95% CI: 55%, 67%) in patients with severe/very severe VOD/SOS. TESAEs of interest occurred in 29% of these patients; VOD/SOS-related mortality at 12 months was 15%. DEFIFrance represents the largest collection of real-world data on post-registration defibrotide use, supporting the real-world utility of defibrotide for patients with severe/very severe VOD/SOS post-HCT.

Mots clés: Drug therapy; Haematopoietic stem cells

Domaines: Médecine humaine et pathologie

Mohamad Mohty, Didier Blaise, Régis Peffault de Latour, Myriam Labopin, Jean Henri Bourhis, et al.. Real-world use of defibrotide for veno-occlusive disease/sinusoidal obstruction syndrome: the DEFIFrance Registry Study. Bone Marrow Transplantation, 2022, ⟨10.1038/s41409-022-01900-6⟩. ⟨hal-03915550⟩