Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, Therapies
DEFIFrance was an observational, post-marketing study that collected retrospective and prospective data on patients receiving defibrotide at 53 French transplant centers from July 2014 to March 2020. VOD/SOS severity was categorized retrospectively/prospectively using adult EBMT criteria in patients aged ≥18 years, and in patients aged <18 years using pediatric EBMT criteria. EBMT PASS was a multinational, prospective, observational study that enrolled defibrotide-treated patients from April 2015 to July 2018. EBMT PASS investigators graded VOD/SOS severity based on their clinical expertise. Investigators in both registries diagnosed VOD/SOS using classical/standard criteria (including, but not limited, to hyperbilirubinemia, hepatomegaly, ascites, and weight gain >5%). Since VOD/SOS grading was performed differently in the two registries, for this pooled analysis, mild/moderate and severe/very severe cases in DEFIFrance were combined with non-severe and severe cases in EBMT PASS, respectively.
Overall, 414 defibrotide-treated patients with VOD/SOS post-HCT were included (336 from DEFIFrance and 78 from EBMT PASS). The median (range) time from HCT to VOD/SOS diagnosis was 13 (interquartile range [IQR]: 8, 21) and 14 (IQR: 8, 22) days in patients with severe and non-severe VOD/SOS, respectively. Median time to initiation of defibrotide treatment after VOD/SOS diagnosis was 0 days in both severe (IQR: 0, 1) and non-severe (IQR: 0, 1) patients. 301/414 patients (73%) had resolution of VOD/SOS. Among those with severe and non-severe VOD/SOS, respectively, 208/302 (69%) and 91/108 (84%) had VOD/SOS resolution; 2 patients had missing severity data. Median time from start of defibrotide treatment to VOD/SOS resolution was 20 days (range: 3, 110) in patients with severe VOD/SOS and 15 days (range: 1, 147) in patients with non-severe VOD/SOS. Median treatment duration among patients with severe and non-severe VOD/SOS was 16.5 days (range: 1, 258) and 16 days (range: 3, 73), respectively. Among patients with resolution of VOD/SOS, symptoms resolved after Day 21 in 36% of patients with severe VOD/SOS and 23% of patients with non-severe VOD/SOS. Kaplan-Meier (KM)-estimated survival at Day 100 post-HCT among patients with severe VOD/SOS was 84% (95% confidence interval [CI]: 78%, 88%) in those who achieved VOD/SOS resolution and 14% (95% CI: 8%, 22%) in those who did not; among patients with non-severe VOD/SOS, this was 94% (95% CI: 87%, 98%) and 35% (95% CI: 15%, 57%), respectively.
Serious treatment-emergent adverse events (TEAEs) of interest occurred in 25% of patients with VOD/SOS resolution; similar safety outcomes were observed by defibrotide duration (≤21 days [25%] or >21 days [26%]). In patients treated for ≤21 days and >21 days, respectively, the most common serious TEAEs of interest by category were infection (14% and 15%) and hemorrhage (12% and 13%). Among patients with VOD/SOS resolution, the most common causes of death were infection (severe: 11%; non-severe: 2%) and GvHD (severe: 6%, non-severe: 2%).
In conclusion, time to resolution of VOD/SOS tended to be longer in patients with severe versus non-severe disease, with a substantial proportion requiring >21 days of therapy to achieve resolution. Day 100 survival was higher in patients with VOD/SOS resolution versus without, regardless of severity, highlighting the importance of obtaining resolution of VOD/SOS symptoms. The safety profile of defibrotide in the real-world setting was consistent with reports from previous studies, supporting the utility of defibrotide treatment.
Disclosures: Mohty: GSK: Honoraria; Oncopeptides: Honoraria; Pfizer,: Honoraria; Adaptive Biotechnologies: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Gilead: Honoraria; Janssen: Honoraria, Research Funding. Locatelli: Jazz Pharmaceuticals: Honoraria; BlueBird bio: Speakers Bureau; Miltenyi: Speakers Bureau; Medac: Speakers Bureau; Neovii: Speakers Bureau; Amgen: Speakers Bureau; SOBI: Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Peffault De Latour: Samsung: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria; Keocyte: Consultancy, Honoraria; Jazz: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Sobi: Consultancy, Honoraria. Labopin: Jazz Pharmaceuticals: Honoraria. Amber: Jazz Pharmaceuticals: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Gutierrez: Jazz Pharmaceuticals: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Dronamraju: Jazz Pharmaceuticals: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Dalle: Novartis: Honoraria; Vertex: Honoraria; Sanofi: Honoraria; Medac: Honoraria; Orchard: Honoraria; Teva: Current equity holder in private company; Jazz Pharmaceuticals: Honoraria. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria.
OffLabel Disclosure: The abstract describes outcomes in patients with non-severe VOD/SOS, who are not included in the indicated population in the product label
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