Real-World Wutcome of Defibrotide for Treatment of Adult Patients Who Developed Severe Hepatic VOD/SOS after Allogeneic Hematopoietic Cell Transplantation

Background: Hepatic veno-occlusive disease/ sinusoidal obstruction syndrome (VOD/SOS) is a rare but severe complication after hematopoietic cell transplantation (HCT) showing high fatality. Recently reported incidence of VOD/SOS in the Korea was 8.9% (7.8% in adults and 14.0% in pediatrics). Estimated 1-year overall survival (OS) of VOD/SOS was around 41% and the outcome was much dismal when it progressed to severe (36.8%) or very severe grade VOD/SOS (5.7%) based on the revised EBMT severity criteria. Defibrotide (DF) is the only approved agent for the treatment of severe to very severe VOD/SOS, and we tried to analyze the real-world outcome in Korea.

Methods: DF was approved in Korea since 2016, and we tried to retrospectively analyze the outcome of severe to very severe VOD/SOS treated with defibrotide from 2016 to 2023. Totally 73 adult patients were identified. DF was indicated in Korea in patients who satisfied 4 or more out of 6 severity parameters - Time from diagnosis to VOD, total bilirubin, bilirubin doubling time, elevation of aminotransferase, weight gain, and decreased renal function, which was amended to 2 or more out of 5 parameters (excluding weight gain). The diagnosis the severity was assessed by revised EBMT criteria.

Results: Median time from HCT to VOD/SOS diagnosis was 21 days (range D-1 to D+414), and the median time from diagnosis to defibrotide was 1 day (range 0 to 40). There were 40 severe and 33 very severe VOD/SOS at DF start, and they progressed to 20 severe and 53 very severe at worst period (WP). Overall response was observed in 34 (46.5%), and complete resolution (CR) was in 29 (39.7%) - 52.5% in severe and 24.2% in very severe. OS at 100-day was 34.2% (40.3% for severe-DF and 26.4% for very severe-DF, while 62.4% for severe-WP and 23.2% for very severe-WP, p<0.001). When only based on the total bilirubin level (<3, 3-5, 5-8, >8mg/dL), the CR rate (71.4%, 50%, 42.9%, and 25%) and 3-year OS (100%, 25%, 16.7%, and 13.2%) were well distinguished to predict prognosis. We also identified that early DF application within 2 days showed higher CR (55.6% vs. 30.4%) and better OS (37.0% vs. 26.1%).

Conclusion: Real-world outcome of defibrotide demonstrated early administration according to current indications showed good therapeutic effects.

Park:ImpriMed, Inc.: Consultancy, Current holder of stock options in a privately-held company. Kim:AbbVie, Astellas, BMS, Handok, Novartis, AML-Hub, Jazz Pharmaceuticals and Takeda: Honoraria, Speakers Bureau; AML-Hub, APBMT, ICBMT, APLC, Novartis and BMS: Other: and leadership or fiduciary roles in other board, society, committee or advocacy group ; Jazz Pharmaceuticals, Takeda, Astellas, AbbVie and APLC: Other: Travel; BMS & Celgene, Novartis, APLC, AbbVie, Astellas, Janssen, Handok, Pfizer, Sanofi Genzyme, AML-Hub, Daiichi Sankyo and APBMT: Membership on an entity's Board of Directors or advisory committees; AbbVie, AIMS Bioscience, AML-Hub, Astellas, BMS & Celgene, Boryung Pharm Co., Daiichi Sankyo, Janssen, Handok, LG Chem, Novartis, Pfizer, SL VaxiGen, VigenCell, Aston Bioscience, Ingenium, Amgen, Sanofi Genzyme, Takeda, Meiji Pharm Co. and GreenCross Phar: Consultancy; BL&H: Research Funding.