Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome BRITISH JOURNAL OF HAEMATOLOGY Kernan, N. A., Grupp, S., Smith, A. R., Arai, S., Triplett, B., Antin, J. H., Lehmann, L., Shore, T., Ho, V. T., Bunin, N., Iacobelli, M., Liang, W., Hume, R., Tappe, W., Soiffer, R., Richardson, P. 2018; 181 (6): 816–27


Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic stem cell transplant (HSCT) conditioning and chemotherapy. Defibrotide is approved for treatment of hepatic VOD/SOS with pulmonary or renal dysfunction [i.e., multi-organ dysfunction (MOD)] after HSCT in the United States and severe VOD/SOS after HSCT in patients aged older than 1 month in the European Union. Defibrotide was available as an investigational drug by an expanded-access treatment programme (T-IND; NCT00628498). In the completed T-IND, the Kaplan-Meier estimated Day +100 survival for 1000 patients with documented defibrotide treatment after HSCT was 58·9% [95% confidence interval (CI), 55·7-61·9%]. Day +100 survival was also analysed by age and MOD status, and post hoc analyses were performed to determine Day +100 survival by transplant type, timing of VOD/SOS onset (=21 or >21 days) and timing of defibrotide treatment initiation after VOD/SOS diagnosis. Day +100 survival in paediatric patients was 67·9% (95% CI, 63·8-71·6%) and 47·1% (95% CI, 42·3-51·8%) in adults. All patient subgroups without MOD had higher Day +100 survival than those with MOD; earlier defibrotide initiation was also associated with higher Day +100 survival. The safety profile of defibrotide in the completed T-IND study was similar to previous reports.

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