Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster II
Hematology Disease Topics & Pathways:
Biological, Therapies, transplantation
This post-marketing study collected retrospective and prospective real-world data on patients receiving defibrotide at 53 HCT centers in France from July 15, 2014 to March 31, 2020. VOD/SOS severity was categorized using European Society for Blood and Marrow Transplantation criteria (adults) or study steering committee member adjudication (pediatric patients). The primary endpoints included Kaplan-Meier (KM)–estimated Day 100 (post-HCT) survival and Day 100 complete response (CR; total serum bilirubin <2 mg/dL and MOF resolution per investigators’ assessment) in patients with severe/very severe VOD/SOS post-HCT. Secondary endpoints included evaluation of adverse events (AEs) of interest, such as hemorrhage, coagulopathy, injection-site reactions, infections, and thromboembolic events, irrespective of their relationship to treatment.
Of the 775 defibrotide-treated patients included in the study analysis, 250 received defibrotide for the treatment of severe/very severe VOD/SOS post-HCT (severe: 119 [48%]; very severe: 131 [52%]). The median patient age was 45 years (range: 5 months, 74 years) and 52 (21%) patients were less than 18 years of age. A total of 219 (88%) patients had received allogeneic HCT and 95 (38%) patients had an unrelated donor. The Day 100 KM-estimated survival was 58% (95% confidence interval [CI]: 52%, 64%) in patients with severe/very severe VOD/SOS post-HCT. The estimated Day 100 survival rate was higher in patients with severe (74% [95% CI: 65%, 81%]) versus very severe (43% [95% CI: 35%, 52%]) VOD/SOS. Among patients with severe/very severe VOD/SOS post-HCT, the CR rate at Day 100 was 53% (95% CI: 47%, 59%). The Day 100 CR rate was higher in patients with severe (68% [95% CI: 60%, 77%]) versus very severe (39% [95% CI: 30%, 47%]) VOD/SOS. Treatment emergent AEs of interest occurred in 41% of patients with severe/very severe VOD/SOS, with infection (23%) and bleeding (17%) being the most commonly reported.
The DEFIFrance study represents the largest collection of real-world data on the use of defibrotide. The effectiveness and safety observed in this study build upon prior studies supporting the utility of defibrotide for treating severe/very severe VOD/SOS post-HCT in a real-world setting. Among patients receiving defibrotide for VOD/SOS post-HCT, outcomes were better in patients with severe versus very severe disease, highlighting the importance of early diagnosis and treatment of VOD/SOS before patients reach the most severe stage of VOD/SOS.
Disclosures: Mohty: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau. Yakoub-Agha: Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Jazz Pharmaceuticals: Honoraria; Janssen: Honoraria. Labopin: Jazz Pharmaceuticals: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Renard: Jazz Pharmaceuticals: Research Funding. Jubert: Jazz Pharmaceuticals: Research Funding. Ryan: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Bouvatier: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Dalle: Bellicum: Consultancy, Honoraria; Sanofi-Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Consultancy, Honoraria; Gilead: Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orchard: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Peffault De Latour: Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.