iwCLL 2015: Dr. Constantine Tam on Venetoclax for CLL

While at the 2015 International Workshop in CLL last September, I had the opportunity to talk with Dr. Tam, from The Sir Peter MacCallum Department of Oncology at the University of Melbourne in Australia. He is a long time CLL researcher who has been one of the leaders in the charge of leveraging our cancers cells’ dependence on BCL-2 to survive when by all rights, they should be committing suicide. Venetoclax (formerly ABT-199) is a potent blocker of the BCL-2 survival pathway and a powerful killer of CLL cells, but has little effect on other normal cells.

Take Away Points

• Venetoclax can be understood as a controlled detonation, like those used to take down a building.
• Because it is so potent, it can kill too many cancer cells at once, causing tumor lysis syndrome (TLS) that can lead to overburdening the kidneys and heart with sometimes fatal consequence
• A very slow dose escalation has almost completely eliminated this risk.
• Monotherapy response rates are 80% and complete responses (CR) are achieved for 1 of 4
• In combination with rituximab, CR are achieved by 41% and about half of those are MRD negative.

There is much more detail in the video. Dr. Tam discusses his experience including the adverse events, the durability of response, and the remarkably positive prognosis of those who relapse with CLL or Richter’s Transformation. There are some pleasant surprises.

I suggest that you listen to the end.

Brian Koffman, MD  2/15/16