Defibrotide for the Treatment of Veno-Occlusive Disease Post SCT: Preliminary Results of EU Compassionate Use Program in 332 Patients Confirm Promising Activity and Manageable Toxicity

Introduction: Hepatic veno-occlusive disease (VOD) is one of the most significant regimen-related toxicities of stem cell transplantation (SCT), which when complicated by multi-organ failure (MOF) has a case fatality rate >90%. Defibrotide (DF) is a polydisperse oligonucleotide, with anti-thrombotic, anti-ischemic and thrombolytic properties, especially on microvasculature. Results in earlier studies of DF therapy for VOD/MOF have consistently shown manageable toxicity with promising complete response (CR) rates and D+100 survival post SCT. We report the results of the largest compassionate use program (CUP) performed to date. Methods: Physicians in Europe requesting DF for the treatment of pts with VOD obtained the drug on a named patient basis and were requested to collect data by a standardized CRF. Patients (pts) were reviewed to identify the nature and frequency of Suspected Adverse Drug Reactions (SADR). CR and D+100 survival post-SCT were assessed with CR defined as bilirubin Conclusions: In this largest study of pts treated with DF to date, no unexpected toxicities were reported and side effects were generally manageable. CR was obtained in 52% with D+100 survival in 46%, including 34% in those pts with severe disease. This is consistent with prior studies and suggests that DF offers a relatively safe and effective treatment for hepatic VOD post SCT.