EHA 2015
Comment: Venetoclax with rituxumab highly active in relapsed refractory CLL
Prof Anton Hagenbeek - University Medical Center Utrecht, Utrecht, Netherlands
In relapsed and refractory chronic lymphocytic leukaemia we’ve been hearing from Dr Roberts about a new approach that uses a new substance that actually targets BCL-2. Can you explain this to me, first of all, and then I want to know what you think about it.
BCL-2 is a gene that is expressed through a translocation, chromosomes that exchange small pieces in chronic lymphocytic leukaemia. The BCL-2 gene, when it gets to expression it prevents programmed cell death. That is the major issue in chronic lymphocytic leukaemia, those cells are not proliferating rapidly but they are not going to die. They pile up due to the BCL-2 expression. It prevents programmed cell death.
And what has venetoclax done, then?
It blocks the activity of the BCL-2 protein so thereby it again stimulates your programmed cell death, the so-called apoptosis, and has been shown to be quite effective in a disease like chronic lymphocytic leukaemia.
Now Andrew Roberts described this as highly active and it offers a chemotherapy-free regimen. What do you make of those claims?
Exactly. I think that’s also one of the new developments, to try to get rid and stay away from conventional cytotoxic drugs with all their early and late side effects and go for more intelligent combinations of immunotherapy like rituximab, an anti-CD20 antibody killing CLL cells, with this BCL-2 protein inhibitor which could be introduced after, we found out what the pathway is through which the CLL cell keeps alive. So it’s intelligent combination of these new molecules that are either targeting an antigen or targeting a pathway through which the cells becomes more vulnerable and can die.
What do you think is the bottom line for doctors, then?
Again here it’s not still in standard practice, venetoclax, but it will certainly get there based on these sort of studies and randomised studies that are ongoing. I think there’s a great future for these sorts of targeted drugs in this case, inhibiting the BCL-2 protein.
