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Preparing for HSCT
Photo by Chad McNeeley

SAN DIEGO—Results of 3 studies appear to support the use of defibrotide in patients who develop hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplant (HSCT).

Defibrotide is the sodium salt of a complex mixture of single-stranded oligodeoxyribonucleotides derived from porcine mucosal DNA. It has antithrombotic, anti-inflammatory, and anti-ischemic properties.

The drug is already approved in Europe to treat VOD and is under investigation for this indication in the US.

Researchers presented data from 3 studies showing promising results with defibrotide at the 2015 BMT Tandem Meetings. The studies were sponsored by Jazz Pharmaceuticals, the company developing defibrotide.

T-IND study

Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston, presented data from an ongoing treatment investigational new drug (T-IND) study (abstract 111*).

The study included 641 patients with VOD who received at least one dose of defibrotide—279 who had severe VOD with multi-organ failure (MOF), 247 who had VOD without MOF, and 526 who had undergone HSCT.

Twenty-one percent of patients had at least 1 treatment-related adverse event (AE). Common treatment-related AEs included hypotension (13%), respiratory failure (8%), diarrhea (8%), pyrexia (7%), pulmonary hemorrhage (7%), renal failure (7%), vomiting (6%), gastrointestinal hemorrhage (6%), hypoxia (6%), epistaxis (5%), and nausea (5%).

At day 100 in post-HSCT patients, the overall survival rate was 52%. The rate was 45% among patients with MOF, and 60% among patients without MOF.

Dr Richardson concluded that defibrotide was generally well-tolerated, and the survival results were favorable. He noted that the higher survival rate in patients without MOF indicates a need to study the impact of treatment earlier in the course of VOD.

NNT study

Dr Richardson also presented data from a number needed to treat (NNT) analysis from a historically controlled, phase 3 trial in patients undergoing HSCT (abstract 112).

For this study, researchers used data from the phase 3 trial to evaluate the NNT with defibrotide to achieve 1 complete response (CR) or to prevent 1 death at day 100 after HSCT in patients with severe VOD (n=102) compared with untreated, historical controls (n=32).

At 100 days, 23.5% of patients in the defibrotide cohort had a CR, compared to 9.4% of historical controls (P=0.013). Survival at 100 days was 38.2% in the defibrotide cohort and 25% among historical controls (P=0.034).

Based on these data, the NNT to achieve 1 CR with defibrotide by day 100 was 7, and the NNT to prevent 1 death at day 100 was 8.

Dr Richardson concluded that defibrotide demonstrated improved CR and survival in patients with severe VOD. And the NNTs with defibrotide are comparable to or lower than those with other therapeutic medical interventions in critical care.

Compassionate use program

Selim Corbacioglu, MD, of the University of Regensburg in Germany, presented final results of an international compassionate use program for defibrotide (abstract 109).

The program included 710 patients who received at least 1 documented dose of defibrotide. In all, 628 patients had undergone HSCT, 429 had severe VOD, and 292 had MOF.

Twenty-eight percent of patients discontinued treatment with defibrotide. Fifty-three percent of patients had AEs, 18% of which were possibly treatment-related. These were primarily gastrointestinal hemorrhage (2%), hemorrhage (1%), and pulmonary hemorrhage (1%).

At day 100 (post-HSCT, chemotherapy, or radiation), the survival rate was 54%. Survival varied according to defibrotide dose. It was 43% for the 10 mg/kg/day group, 58% for the 25 mg/kg/day group, 54% for the 40 mg/kg/day group, 61% for the 60/80 mg/kg/day group, and 51% for patients whose dose was unknown.

Dr Corbacioglu noted that the side-effect profile and the survival rates in this program were consistent with those observed in prior defibrotide studies. And these data support 25 mg/kg/day as the optimal dose of the drug. end hematology article

*Information in the abstract differs from that presented at the meeting.

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