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.

References:

  1. BESPONSA® SmPC Summary of Marketing Product Characteristics
  2. Kantarjian HM, et al. New Engl J Med. 2016;375:740-53.
  3. Mohty M, et al. Bone Marrow Transplant. 2015;50:781-9.
  4. Mohty M, et al. Bone Marrow Transplant. 2016;51:906-12. 
  5. Defitelio (defibrotide) SmPC 2016.

PP-INO-GBR-0133. May 2020