In another audio interview from ASCO 2014, I spoke with the ubiquitous Dr. Jeff Sharman about data from the clinical trial studying two different doses of single-agent obinutuzumab, which is a fully humanized monoclonal type II antibody directed against CD20, also known as GA101 and upon FDA approval, the brand name Gazyva. CD20 is the same target used by rituximab and ofatumumab. Dr. Sharman heads up a large national CLL/NHL research group has brought us several important clinical results that has advanced our understanding of treatment options and provides direction for further research.
The abstract with lead author Dr. Joe Flynn showed a strong trend to a better response with the higher dose, especially as regards complete responses. This is not surprising when we know from a dose escalation trial of rituximab published in 2001 from Dr. Susan O’Brien (mentioned in the interview by Dr. Sharman), that when it comes to antibodies, more is better.
Makes sense based on what we know about how these antibodies work. There are billions of B cells and only so much antibody. When they are all “bound up”, there are none left.
There is also research now looking to see if there is a similar dose response relation with CAR-T therapy: the more chimeric T-cells, the better, though the story here is much more complicated as it seems CAR-T cells are serial killers.
Dr. Kipps and I also discussed this same paper and the difference between Type 1 and Type 2 antibodies here. Dr. Jennifer Brown discusses earlier research on GA101 (obinutuzumab) at ASH 2013 and the different types of antibodies here. And here are the details of its FDA approval and some of my comments only published only a little more than a year ago.
And if that’s not enough background, here is an editorial from Blood 2012.
What a great year it has been for those of us touched by CLL! We are all on a fast moving train and while cure is still a distant light in the tunnel, long lasting low toxicity disease control for most of us may be a whistle stop that we blew past some time ago without even noticing some time last year.
Enjoy the audio interview with Dr. Sharman.
Thank you for putting up with all the pops and hisses again.
Dr. Brian Koffman 11/29/14