In a real-world study, defibrotide appeared useful in treating patients with severe/very severe veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). This is based on results presented in a poster at the 2022 Tandem Meetings by Mohamad Mohty, MD, of the Université of Sorbonne in Paris, France, and colleagues.
VOD/SOS is a possibly fatal condition that can arise as a complication of hematopoietic cell transplantation (HCT) conditioning or use of high-dose chemotherapy, and it is associated with sinusoidal endothelium damage. Defibrotide is an agent that acts to protect and stabilize endothelial lining, Dr Mohty and colleagues explained in their poster.
The study was the DEFIFrance study, a postmarketing registry study in which patients with VOD/SOS after HCT were treated with defibrotide at 53 HCT centers across France. The severity of the VOD/SOS was determined using adult or pediatric European Society for Blood and Marrow Transplantation criteria based on patient age. The primary study endpoints included day-100 post-HCT survival and complete response (CR) rates for patients who had severe/very severe VOD/SOS. Treatment-emergent serious adverse events (TESAEs) of interest were evaluated as a secondary endpoint.
A total of 798 patients received defibrotide, with 251 of these patients categorized as having severe/very severe VOD/SOS following HCT. VOD/SOS was severe in 47% and very severe in 53%. Patients in the study had a median age of 45 years (range, 0-74), with 23% being younger than 18 years. Acute myeloid leukemia was the primary diagnosis in 27% of patients, and acute lymphoblastic leukemia was the primary diagnosis in 20%.
The day-100 survival rate after HCT was 61% (95% CI, 55%-67%) for patients who had severe/very severe VOD/SOS. The 6-month post-HCT survival rate was 50%, and the 12-month rate was 43%, among patients with severe/very severe VOD/SOS. Patients with severe VOD/SOS had higher survival rates than those with very severe VOD/SOS did at each of these time points. At 12 months, the survival rate with severe VOD/SOS was 54% (95% CI, 44%-62%), compared with 33% (95% CI, 25%-41%) in patients with very severe VOD/SOS.
The day-100 CR rate was estimated to be 74% for patients with severe/very severe VOD/SOS. Additionally, at day 100, 55% of the population with severe/very severe VOD/SOS was alive and in CR. Day-100 CR was 84% for patients whose VOD/SOS was severe, and it was 63% for those with very severe VOD/SOS.
The rate of any TESAEs of interest in patients with severe/very severe VOD/SOS was 29%. The most common categories of TESAEs reported in ≥2% of patients were infection (in 17% of patients), hemorrhage (in 16%), and hypotension (in 2%). The 12-month cumulative incidence of death owing to VOD/SOS was 15%.
Dr Mohty and colleagues concluded that results from this study support the utility of defibrotide in patients with severe/very severe VOD/SOS following HCT. They also considered patients treated with defibrotide who had severe, rather than very severe, VOD/SOS to fare better, signifying the importance of prompt diagnosis and management.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
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Mohty M, Blaise D, Peffault de Latour R, et al. Final long-term results from the Defifrance Registry Study: efficacy and safety of defibrotide (DF) for the treatment of severe/very severe veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after hematopoietic cell transplantation (HCT). Presented at: 2022 Tandem Meetings; April 23-26, 2022; Abstract 181.