DEFIFrance: Real-world use of defibrotide for VOD/SOS

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is believed to result from endothelial cell activation and injury, induced by toxic metabolites generated from haematopoietic cell transplantation (HCT) regimens. Defibrotide can act as an endothelial cell protector and stabiliser. The DEFIFrance post-marketing registry study investigated real-world data on the efficacy and safety of defibrotide from HCT centres in France.

DEFIFrance collected retrospective and prospective real-world data on patients receiving defibrotide at 53 French HCT centres. Diagnosis of VOD/SOS was determined at the investigator's discretion using standard criteria, in line with typical clinical practice. Disease severity was categorised according to the adult EBMT severity criteria for patients aged 18 years and older, while patients under 18 years were categorised retrospectively or prospectively using the pediatric EBMT severity criteria. The primary endpoints included survival and complete response (CR) 100 days after HCT. A secondary endpoint was the evaluation of treatment-emergent serious adverse events (TESAEs) of interest.

Key findings

1. Positive outcomes in terms of survival and complete response rates at Day 100 post-HCT in patients with severe/very severe VOD/SOS:
   
   • KM-estimated CR at day 100 post-HCT was 74% (95% CI 66-81%)
     
   • KM-estimated survival at day 100 post-HCT was 61% (95% CI 55-67%)
2. Treatment-emergent serious adverse events (TESAEs) occurred in 29% of patients with severe/very severe VOD/SOS, with VOD/SOS-related mortality at 12 months being 15%.
3. The study highlighted the real-world utility of defibrotide for patients with severe/very severe VOD/SOS post-HCT, supporting its effectiveness and safety in this patient population.
4. The study emphasised the importance of early diagnosis and treatment of VOD/SOS before patients reach the most severe stage, underscoring the critical need for prompt intervention in these life-threatening conditions.
5. The results suggested that defibrotide prophylaxis may be beneficial in reducing the incidence of VOD/SOS by Day 30 post-HCT in high-risk patients, although further controlled studies are needed to confirm these findings.
6. The study provided valuable insights into the heterogeneous and dynamic nature of VOD/SOS symptoms, highlighting the challenges in diagnosing and managing this condition, especially in patients who do not exhibit all classical features of the disease.

The DEFIFrance Registry study contributed to the largest collection of real-world data on the post-registration use of defibrotide, adding to the existing evidence supporting the utility of defibrotide in treating paediatric and adult patients with severe/very severe VOD/SOS post-HCT.

Read the full published article:
Mohty M, et al. Real-world use of defibrotide for veno-occlusive disease/sinusoidal obstruction syndrome: the DEFIFrance Registry Study. Bone Marrow Transplant. 2023;58(4):367-376. https://doi.org/10.1038/s41409-022-01900-6.

 



Posted on 17 July 202417 July 2024