ASH 2014: Professor Roberts Explains How Venetoclax Works in CLL

At the 2014 American Society of Hematology annual meeting in San Francisco, Professor Andrew Roberts from the Walter and Eliza Hall Institutes of Medical Research in Melbourne, Australia provided an overview of how ABT-199 or venetoclax works, as well as the risks and benefits of treatment for chronic lymphocytic leukemia (CLL).

Take Away Points:

• BCL-2 is overproduced in CLL and makes it much harder to kill CLL cells.
• ABT-199 or venetoclax is a potent inhibitor of BCL-2  which leads to rapid cell death.
• Early dosing trials of ABT-199 or venetoclax lead to several instances of fatal tumor lysis syndrome (TLS).
• Subsequent changes in dosing have greatly lower the risk of TLS.
• Early results show 80% total response rates and even more amazingly, a 20% complete response in relapsed and refractory disease using monotherapy with this oral medicine.

ASH 2014:

Professor Roberts provides some history of how we discovered the importance of high levels of the protein BCL-2 in preventing cell death by apoptosis (programmed cell death or “cell suicide”) in CLL and the development of a drug to specifically target and knock out that defensive pathway in our cancer cells.

He goes on to share some of the early concerns and subsequent adjustments in dosing.

(Revisit this blog post for my real time reactions to those tragic events and their consequences as the story unfolded. Search for ABT-199 on my blog to follow the whole tale).

Finally, Prof. Roberts shares the early results of monotherapy with ABT-199 or venetoclax.

Here is the first part of the ASH 2014 interview with Prof. Roberts.

Dr. Brian Koffman 5/3/2015