> Details
Mohty, Mohamad;
Blaise, Didier;
Peffault De Latour, Regis;
Labopin, Myriam;
Detrait, Marie;
Girault, Stephane;
Huynh, Anne;
Labussière-Wallet, Hélène;
Lamy, Thierry;
Lebon, Delphine;
Maury, Sébastien;
Renard, Cecile;
Asubonteng, Kobby;
Delaval, Floriane;
Yakoub-Agha, Ibrahim;
Dalle, Jean-Hugues
Final Long-Term Results from the Defifrance Registry Study: Efficacy and Safety of Defibrotide for the Treatment of Severe/Very Severe Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation
Sharing
Reference
management
Direct link
Bookmarks
Remove from
bookmarks
Share this by email
Share this on Twitter
Share this on Facebook
Share this on Whatsapp
- Media type: E-Article
- Title: Final Long-Term Results from the Defifrance Registry Study: Efficacy and Safety of Defibrotide for the Treatment of Severe/Very Severe Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation
- Contributor: Mohty, Mohamad; Blaise, Didier; Peffault De Latour, Regis; Labopin, Myriam; Detrait, Marie; Girault, Stephane; Huynh, Anne; Labussière-Wallet, Hélène; Lamy, Thierry; Lebon, Delphine; Maury, Sébastien; Renard, Cecile; Asubonteng, Kobby; Delaval, Floriane; Yakoub-Agha, Ibrahim; Dalle, Jean-Hugues
-
imprint:
American Society of Hematology, 2021
- Published in: Blood
- Language: English
- DOI: 10.1182/blood-2021-147302
- ISSN: 0006-4971; 1528-0020
- Keywords: Cell Biology ; Hematology ; Immunology ; Biochemistry
- Origination:
- Footnote:
- Description: <jats:title>Abstract</jats:title> <jats:p>Introduction: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT) conditioning that may also develop after high-dose chemotherapy. Multiorgan failure (MOF) is associated with the most severe form of VOD/SOS and, if untreated, may result in a mortality rate of &gt;80%. Defibrotide is approved for the treatment of hepatic VOD/SOS with renal or pulmonary dysfunction post-HCT in the US and for severe hepatic VOD/SOS post-HCT in patients aged &gt;1 month (mo) in the EU. The DEFIFrance study collected real-world data on the efficacy and safety of defibrotide from HCT centers in France. This analysis presents final, long-term data on the primary study population: patients who received defibrotide treatment for severe/very severe VOD/SOS post-HCT.</jats:p> <jats:p>Methods: This post-marketing registry study collected retrospective and prospective real-world data on patients receiving defibrotide at 53 HCT centers in France. Diagnosis of VOD/SOS was at the investigator's discretion using standard criteria, per typical clinical practice. Disease severity was categorized using adult EBMT severity criteria in patients aged ≥18 years (y), and patients aged &lt;18 y were retrospectively/prospectively categorized using pediatric EBMT severity criteria. The primary endpoints were Day 100 post-HCT survival and complete response (CR; total serum bilirubin &lt;2 mg/dL and MOF resolution per investigators' assessment) in patients with severe/very severe VOD/SOS. A secondary endpoint was the evaluation of treatment-emergent serious adverse events (SAEs) of interest: hemorrhage, coagulopathy, injection-site reactions, infections, and thromboembolic events, irrespective of relationship to treatment.</jats:p> <jats:p>Results: Of 798 defibrotide-treated patients enrolled in the study, 251 patients received defibrotide for the treatment of severe/very severe VOD/SOS post-HCT (severe: 117 [47%]; very severe: 134 [53%]). Median age was 45 y (range: 0, 74) and 58 (23%) patients were &lt;18 y of age. The most common primary diagnoses were acute myeloid leukemia (68 [27%]) and acute lymphoblastic leukemia (49 [20%]). Common (&gt;50%) risk factors included prior treatment with hepatotoxic drugs (150 [60%]), iron overload (133 [58%]), and relapsed/refractory disease (137 [55%]). Risk factors of interest included prior HCT (29/239 [12%]), and prior treatment with gemtuzumab ozogamicin (17/251 [7%]) and inotuzumab ozogamicin (6/251 [2%]). At diagnosis, 55/250 (22%) patients had anicteric VOD/SOS (bilirubin levels ≤2 mg/dL). Median (range) time from VOD/SOS diagnosis to defibrotide administration was 0 (-1, 24) days.</jats:p> <jats:p>The Kaplan-Meier (KM)-estimated Day 100 post-HCT survival rate was 61% (95% confidence interval [CI]: 55%, 67%) in patients with severe/very severe VOD/SOS, with a higher survival rate seen in patients with severe versus very severe disease. The post-HCT survival rate in patients with severe/very severe VOD/SOS was 50% at 6 mo and 43% at 12 mo (Figure). KM-estimated survival rates at 6 and 12 mo were also higher for those with severe versus very severe disease (Figure). The KM-estimated CR rate by Day 100 among patients with severe/very severe VOD/SOS post-HCT was 74% (95% CI: 66%, 81%). Similar to the pattern observed for the survival rate, a higher CR rate was observed by Day 100 in patients with severe (84% [95% CI: 74, 92]) versus very severe (63% [95% CI: 52, 74]) VOD/SOS.</jats:p> <jats:p>Treatment-emergent SAEs of interest occurred in 29% of patients with severe/very severe VOD/SOS post-HCT; the most common (≥2%) treatment-emergent SAE categories were infection (17%), hemorrhage (16%), and hypotension (2%). Mortality due to VOD/SOS at 12 mo was 15%.</jats:p> <jats:p>Conclusions: The DEFIFrance study represents the largest collection of real-world data on post-registration use of defibrotide. The efficacy and safety observed in this study add to evidence from prior studies supporting the utility of defibrotide for treating patients with severe/very severe VOD/SOS post-HCT in a real-world setting. Among patients receiving defibrotide for VOD/SOS post-HCT, outcomes were better in patients with severe versus very severe VOD/SOS, highlighting the importance of early VOD/SOS diagnosis and treatment, before patients reach the most severe stage of VOD/SOS.</jats:p> <jats:p>Figure 1 Figure 1.</jats:p> <jats:p /> <jats:sec> <jats:title>Disclosures</jats:title> <jats:p>Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Peffault De Latour: Amgen: Consultancy, Other, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Jazz Pharmaceuticals: Honoraria. Labopin: Jazz Pharmaceuticals: Honoraria. Detrait: Jazz Pharmaceuticals: Research Funding. Huynh: Jazz Pharmaceuticals: Honoraria. Renard: Jazz Pharmaceuticals: Research Funding. Asubonteng: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Delaval: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Dalle: Jazz Pharmaceuticals: Honoraria.</jats:p> </jats:sec>
- Access State: Open Access