PF747 DEFIBROTIDE TREATMENT IN ADULTS WITH SEVERE OR VERY SEVERE VENO‐OCCLUSIVE DISEASE/SINUSOIDAL OBSTRUCTION SYNDROME AFTER HEMATOPOIETIC CELL TRANSPLANTATION: DEFIFRANCE STUDY INTERIM RESULTS
Authors: I. Yakoub‐Agha, M. Labopin, D. Blaise, R. Peffault de Latour, V. Bouvatier, A. Petitprez, M. Mohty
Journal: HemaSphere (2019)

Background: Hepatic veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication after hematopoietic cell transplantation (HCT) and may also develop after high‐dose chemotherapy alone. Severe VOD/SOS is often accompanied by multi‐organ failure (MOF) and is associated with a mortality rate of &gt;80% when managed with supportive care alone. Defibrotide is approved for the treatment of severe hepatic VOD/SOS post‐HCT in patients aged &gt;1 month in the European Union and for hepatic VOD/SOS with renal or pulmonary dysfunction post‐HCT in the United States and Canada. The DEFIFrance study is being performed to collect real‐world data on safety and efficacy of defibrotide in a broad patient population in France, including adult and pediatric patients. Aims: The goal of this interim analysis of the DEFIFrance study was to evaluate the safety and efficacy of defibrotide for the treatment of VOD/SOS in the subgroup of adult patients who received HCT, using the European Society for Blood and Marrow Transplantation (EBMT) diagnostic and severity criteria. Methods: DEFIFrance is an ongoing multicenter, post‐marketing study that is collecting safety and efficacy data on patients treated with defibrotide at HCT centers in France since July 2014. The data cut‐off for this analysis was 8 November 2018. VOD/SOS severity was categorized retrospectively and prospectively using the EBMT criteria (Mohty M, et al. Bone Marrow Transplantation . 2016;51[7]:906–912). Primary endpoints include the rates of Kaplan‐Meier–estimated Day 100 (post‐HCT) survival and Day 100 complete response (CR; total serum bilirubin &lt;2 mg/dL and resolution of MOF based on the investigators’ assessment). Results: A total of 324 patients treated with defibrotide at 36 active HCT centers in France were included in the DEFIFrance study as of 8 November 2018, including 120 patients diagnosed with VOD/SOS post‐HCT. Of these, 66 adults had severe/very severe VOD/SOS post‐HCT and were included in the current subgroup analysis. The median age was 54 (range, 18–73) years. Median time to onset of VOD/SOS post‐HCT, was 11 (range, −2–76) days. MOF was present in 32 (49%) patients. Fifteen of 26 (58%) patients with renal failure underwent dialysis, and 17/23 (74%) patients with respiratory failure required a ventilator. The Kaplan‐Meier–estimated survival rate at Day 100 post‐HCT was 47%, and the CR rate at Day 100 post‐HCT was 43% ( Figure ). The estimated Day 100 survival rates were 77% and 28% among adults with severe VOD/SOS (n = 26) and very severe VOD/SOS (n = 40), respectively; the Day 100 CR rates were 72% and 25%, respectively. Among adults with severe/very severe VOD/SOS post‐HCT, the overall survival rates were 39% and 31% at 6 months and 12 months post‐HCT, respectively. Mortality related to VOD/SOS was 15% at Day 100; all deaths after Day 100 were considered to be related to a cause other than VOD/SOS. Adverse events (AEs) of interest occurred in 55% of adult patients with severe/very severe VOD/SOS post‐HCT. The most frequently reported AEs of interest included infection (27%), bleeding (21%), and hypotension (6%). Summary/Conclusion: Among adults treated with defibrotide post‐HCT for severe/very severe VOD/SOS, per EBMT criteria, those with severe disease had better outcomes than those with progression to very severe disease, highlighting the potential importance of early VOD/SOS diagnosis and treatment initiation. The incidence of AEs of interest was consistent with that observed in previous defibrotide clinical trials. image