At the 20th Congress of the European Hematology Association (EHA), June 11-15, 2015 in Vienna, Austria, an oral presentation reported more positive data on venetoclax, formerly known as ABT-199 or GDC-199.
Venetoclax works by blocking the amped up pro-survival BCL-2 pathway in our CLL cells leading to rapid cell death in our cancer cells and little other direct damage. For more on this potent drug, how it works on the BCL-2 pathway and its associated benefits and risks, please listen to my interviews with Professor Andrew Roberts from Melbourne, Australia that we did at ASH 2014 here and here.
The response rate of 84% in relapsed and refractory CLL patients is excellent; the complete response rate of 41% is extraordinary; and the fact that almost half the patients were MRD- in the bone marrow is remarkably different than what we usually see with other oral therapies combined with rituximab, however, as Prof. Roberts rightly points out, “Potentially, the most interesting part of these initial results is the data regarding the patients who have been able to come off treatment and who continue to maintain their complete response,”
This is very early data and the numbers are small, but if it turns out to be a high probability, predictable and reliable response in a subset of patients, that would be game changing and a big step towards Prof. Hallek’s goal of a limited duration therapy offering long-term sustained results that he discussed here during our interview at ESH 2014: Prof. Hallek Discusses Trials including Limited Duration Drug Combinations to Move towards a Long Term Control of CLL.
A quick aside and some speculation on my part: We are increasingly seeing some of us get to MRD- status in our bone marrow and blood but our lymph nodes remain stubbornly enlarged. Obviously, the assumption is that the enlarged nodes are still harboring measurable cancer, but at least in a few cases, biopsies of the suspicious nodes have not shown any evidence of residual disease, just normal cells. Maybe they are “ scarred” from the expansion with the cancer, and even when the cancer is gone, they don’t shrink back to normal. This is another area that needs to be researched.
Here is a link to the EHA abstract S431.
Here is a link to a discussion of the abstract included in the Abbvie press release.
Brian Koffman June 27, 2015