Adverse Event Management: VOD/SOS
Veno-occlusive disease occurred more frequently with BESPONSA® than with standard chemotherapy1,2
In the INO-VATE ALL study, VOD/SOS* was reported in 23 patients (14%) treated with BESPONSA®:1,2
- In 5 patients (3%) during or after BESPONSA® treatment without subsequent HSCT (occurring up to 56 days after last dose)1
- There were no cases of VOD among patients in the standard chemotherapy group who did not proceed to HSCT1
- In 18 patients (23%) who proceeded to subsequent HSCT (occurring 3–57 days after transplantation)1
- 5 cases were fatal
- There was 1 (1%) case of VOD after HSCT in the standard chemotherapy group2
In BESPONSA® patients who proceeded to HSCT, the highest risk of VOD/SOS after transplantation was associated with:1
- Use of a HSCT conditioning regimen containing two alkylating agents
- Age ≥ 65 years
- Serum bilirubin ≥ ULN prior to HSCT
*Defined as the occurrence of two or more of the following events: hyperbilirubinaemia (> 34 μmol/L [> 2 mg/dL]); ascites or sudden weight gain (> 2.5%); painful hepatomegaly.1
HSCT, haematopoietic stem cell transplantation; SOS, sinusoidal obstruction syndrome; ULN, upper limit of normal; VOD, veno-occlusive disease.
Other patient factors that appear to be associated with an increased risk of VOD/SOS after HSCT include:1
- Prior HSCT
- Age ≥ 55 years
- History of liver disease and/or hepatitis before treatment
- Later salvage lines
- Greater number of treatment cycles
BESPONSA® is contraindicated in:1
- Hypersensitivity to the active substance or to any of the excipients
- Patients who have experienced prior confirmed severe or ongoing VOD/SOS
- Patients with serious ongoing hepatic liver disease (e.g. cirrhosis, nodular regenerative hyperplasia, or active hepatitis)
More information on VOD is available in the BESPONSA® Therapy Management Guide and from the EBMT published position statement (available online from: https://www.ncbi.nlm.nih.gov/pubmed/25798682)3
EBMT, European Society for Blood and Marrow Transplantation; HSCT, haematopoietic stem cell transplantation; SOS, sinusoidal obstruction syndrome; VOD, veno-occlusive disease.
Veno-occlusive disease recommendations4,5
ALT, alanine aminotransferase; AST, aspartate aminotransferase; EBMT, European Society for Blood and Marrow Transplantation; HSCT, haematopoietic stem cell transplantation; SOS, sinusoidal obstruction syndrome; VOD, veno-occlusive disease.
- BESPONSA® SmPC Summary of Marketing Product Characteristics
- Kantarjian HM, et al. New Engl J Med. 2016;375:740-53.
- Mohty M, et al. Bone Marrow Transplant. 2015;50:781-9.
- Mohty M, et al. Bone Marrow Transplant. 2016;51:906-12.
- Defitelio (defibrotide) SmPC 2016.
PP-INO-GBR-0133. May 2020