Defibrotide effective for veno-occlusive disease after HSCT

April 23, 2022

3 min read

Source/Disclosures

Source:

Mohty M, et al. Abstract 19. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.

Disclosures: Mohty reports honoraria and research funding from Jazz Pharmaceuticals. Please see the abstract for all other researchers’ relevant financial disclosures.

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SALT LAKE CITY — Defibrotide benefitted adults and pediatric patients with severe or very severe veno-occlusive disease/sinusoidal obstruction syndrome after hematopoietic stem cell transplantation, according to study results.

The findings of the DEFIFrance study — presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR — align with previous studies that supported use of the agent in this setting.

infographic showing 1-year survival
Data derived from Mohty M, et al. Abstract 19. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.

“The DEFIFrance study represents the largest collection of real-world data on post-registration use of defibrotide,” Mohamad Mohty, MD, PhD, professor of hematology and head of the hematology and cellular therapy department at Saint-Antoine Hospital and Sorbonne University in Paris, said during a presentation.

“The efficacy and safety observed in this study add to evidence from prior studies supporting the utility of defibrotide for treating pediatric and adult patients with severe/very severe [veno-occlusive disease/sinusoidal obstruction syndrome] [after HSCT] in a real-world setting.”

Background

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication of HSCT. It occurs as a result of activation and damage of the sinusoidal endothelium.

Defibrotide (Defitelio, Jazz Pharmaceuticals) protects endothelial cells and restores the thrombotic-fbrinolytic balance, according to study background.

The agent is approved in the United States for treatment of children or adults with hepatic VOD/SOS with renal or pulmonary dysfunction after HSCT.

Mohty and colleagues conducted DEFIFrance — a post-marketing registry study — to evaluate real-world use of defibrotide for adults or pediatric patients with severe or very severe VOD/SOS after HSCT.

DEFIFrance included 251 patients — 193 adults (median age, 52 years; range, 18-74) and 58 pediatric patients (median age, 6 years; range, 0-18) — treated at 53 centers in France.

A higher percentage of adults than pediatric patients had relapsed/refractory disease (60% vs. 38%) and had received prior HSCT (14% vs. 6%). A comparable percentage of adults and pediatric patients had anicteric VOD/SOS (21 % vs. 26%).

Researchers used European Society for Blood and Marrow Transplantation criteria to categorize VOD/SOS severity.

Primary endpoints included survival at 100 days after HSCT and complete response, defined as total serum bilirubin less than 2 mg/dL and multiorgan failure resolution per investigator assessment.

Secondary endpoints included incidence of treatment-emergent adverse events of interest — including hemorrhages, infections, coagulopathies, injection-site reactions and thromboembolic events — as well as rate of graft-versus-host disease, overall mortality and VOD/SOS-related mortality.

Median time from diagnosis to defibrotide treatment was 0 days in each group (ranges, 0 to10 days in the pediatric cohort and –1 to 24 days among adults).

Efficacy in adult cohort

Among adults, researchers reported estimated 12-month survival of 36% (95% CI, 29-43). A higher percentage of those with severe disease than very severe disease remained alive at 1 year (50% vs. 22%).

An estimated 67% (95% CI, 57-77) achieved complete response by day 100 (81% for severe VOD/SOS vs. 45% for very severe VOD/SOS).

At day 100, 46% of adults remained alive and in complete response.

Efficacy in pediatric cohort

In the pediatric cohort, researchers reported estimated 12-month survival of 65% (95% CI, 51-76). Again, a higher percentage of those with severe disease than very severe disease remained alive at 1 year (71% vs. 62 %).

An estimated 93% (95% CI, 81-98) achieved complete response by day 100 (93% for severe VOD/SOS vs. 91% for very severe VOD/SOS).

At day 100, 84% of pediatric patients remained alive and in complete response.

Safety outcomes

Treatment-emergent adverse events of interest occurred among 32% of adults and 19% of children. The most common events included infection (20% among adults vs. 7% among children), hemorrhage (16% in each cohort) and hypotension (3 % among adults vs. 0% among children).

Adults appeared twice as likely as pediatric patients to die due to VOD/SOS at 12 months (17% vs. 9%).

“Outcomes were better [among] patients with severe vs. very severe VOD/SOS,” Mohty said. “[This] highlights the importance of early VOD/SOS diagnosis and treatment before patients reach the most severe stage of VOD/SOS.”

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