Systematic review of defibrotide studies in the treatment of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS)

Abstract

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) conditioning or high-dose nontransplant chemotherapy. VOD/SOS with multi-organ dysfunction (MOD) is associated with a mortality rate of > 80%. Defibrotide (25 mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States and to treat severe hepatic VOD/SOS in patients > 1 month of age in the European Union. A random effects model was used for pooling data from 17 systematically chosen defibrotide studies. For patients in these reports (n = 2598), and those in the subset of 10 reports of patients treated with~25 mg/kg/day (n = 1691), estimated Day + 100 survival rates were 54% and 56%, respectively. Among those patients treated with~25 mg/kg/day, estimated Day + 100 survival was 44% among patients with MOD and 71% in patients without MOD; survival was 41% and 70%, respectively, for the population of patients receiving any dose of defibrotide. Safety results were not pooled owing to differences in reporting methodology but were generally consistent with the known tolerability profile of defibrotide. This analysis provides the largest assessment of survival in patients treated with defibrotide for VOD/SOS with or without MOD.

Diagnosis and Treatment of VOD/SOS After Allogeneic Hematopoietic Stem Cell Transplantation

“…Data from these important studies are quite superimposable and further confirmed by a systematic review of the literature, which found out 100-day survival of 41% in patients with MOD and 71% in those without MOD (97).…”

Risk Factors for Development of and Progression of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome

“…It is worth noting that defibrotide is currently the sole medication approved for VOD/ SOS [33], and there is little evidence of other emerging therapies for VOD/SOS under development. A pooled analysis of clinical trials found that among HSCT recipients treated for VOD/SOS with defibrotide at or close to the approved dose of 25 mg/kg/day, day +100 survival following HSCT was 56% (95% confidence interval [CI], 49% to 63%) overall, including rates of 44% (95% CI, 35% to 52%) in patients with MOD and 71% (95% CI, 67% to 75%) in patients without MOD [34].…”

Recent developments with defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome

“…In a systematic review of defibrotide studies, a random-effects model was used for pooling data [68]. A total of 10 studies with 1,691 patients who received defibrotide at or close to the approved dosage of 25 mg/kg/day were included.…”

“…For patients with MOD and without MOD, day +100 survival was 44% (95% CI, 35-52%) and 71% (95% CI, 67-75%), respectively. Safety results were not pooled for this review due to differences in how adverse events were reported, but the range of adverse clinical events was consistent with the known safety profile of defibrotide [68]. Similarly, an observational study from the Center for International Blood and Marrow Transplant Research (CIBMTR) reported that patients with severe VOD/SOS who received defibrotide (n = 41) had an improved rate of resolution of VOD/SOS at day +100 (51%) relative to patients not treated with defibrotide (29%; n = 55) [69].…”