55 posters,  8 sessions,  14 topics,  53 authors,  38 institutions
ePostersLive® by SciGen® Technologies S.A. All rights reserved.

CT10
Efficacy and Safety of Defibrotide to Treat Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) Post-Chemotherapy: A Post Hoc Analysis of Final Data of an Expanded-Access Protocol

Poster Presenter
Authors
Affiliations

Rate

No votes yet

Efficacy and Safety of Defibrotide to Treat Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS)
Post-Chemotherapy: A Post Hoc Analysis of Final Data of an Expanded-Access Protocol

Background
•Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable, potentially fatal complication of conditioning regimens for hematopoietic stem cell transplantation (HSCT), but can occur after chemotherapy without HSCT

—VOD/SOS with concomitant multi-organ dysfunction (MOD; eg, renal or pulmonary dysfunction), may be associated with >80% mortality post-HSCT
•Critical factors in the pathophysiology of VOD/SOS include:
—Prior use of cytotoxic regimens
•Chemotherapeutic agents associated with VOD/SOS include inotuzumab, gemtuzumab, 6-thioguanine, and actinomycin-D
—Triggering of endothelial cell (EC) activation and damage, leading to a prothrombotic/hypofibrinolytic state
•Preclinical data suggest that defibrotide reduces EC activation, which protects them from further damage and restores thrombo-fibrinolytic balance
•In the United States (US), defibrotide (25 mg/kg/day divided q6h) is approved for treatment of adult and pediatric patients with hepatic VOD/SOS with renal or pulmonary dysfunction following HSCT

Objective
•To evaluate the efficacy and safety of defibrotide in the expanded-access (T-IND) program among patients with VOD/SOS post-chemotherapy
without HSCT

Methods
PATIENTS
•Prior to approval, defibrotide was available in the US through the T-IND program, the largest prospective study of defibrotide for treatment
of VOD/SOS
—The final protocol included patients with VOD/SOS diagnosed by Baltimore or modified Seattle criteria or biopsy, with or without MOD,
following HSCT or nontransplant-associated chemotherapy
•Key exclusion criteria were clinically significant bleeding and/or need for ≥2 vasopressors
TREATMENT
•All patients received open-label defibrotide as a 2-hour intravenous infusion at 6.25 mg/kg every 6 hours (25 mg/kg/day), recommended
for ≥21 days
ASSESSMENTS
•Original T-IND program followed patients to Day +100 after HSCT
•Presented here is a post hoc survival analysis in the chemotherapy-only subset:
—Patients who initiated defibrotide within 30 days of chemotherapy start day
—Patients were followed for 70 days from start of defibrotide (ie, up to 100 days after chemotherapy initiation)
•New or worsening adverse events (AEs)

Results
PATIENTS
•1154 patients treated with defibrotide in T-IND
•Total of 137 (11.9%) developed VOD/SOS post-chemotherapy without HSCT
—82/137 patients received defibrotide by day 30 after start of chemotherapy (the CHEMO-30 analysis set) and form the basis of this analysis (Table 1)

SURVIVAL
•Figures 1 and 2 show survival by MOD status and age group

SAFETY
•Adverse events (AEs) were reported in 54/82 patients (65.9%; Table 2)

•AEs assessed as being at least possibly related to defibrotide occurred in 22 patients (26.8%; Table 3)
—Related AEs led to discontinuation in 6 patients and were associated with 1 death (pulmonary hemorrhage, hypotension; all patients had MOD)

Conclusions
•Although VOD/SOS is typically associated with HSCT, it also occurs following chemotherapy without HSCT
•Kaplan-Meier estimated survival by Day +70 post first defibrotide dose in the total group was 74.1%, 65.8% in the subgroup with MOD, and 81.3% in the subgroup without MOD
—80.1% in the pediatric subgroup (n=66) and 50.0% in the adult subgroup (n=16)
•The safety profile was consistent with that previously reported and in the overall population of the T-IND program (N=1154)

Enter Poster ID (e.gGoNextPreviousCurrent