ASCO abstracts are out. It feels like Christmas Morning and I am 5 years old (that is probably a very sad commentary about myself).
I'm part way through the CLL stack and Abstract 7041 jumps out at me as a MAJOR discovery:
They took CLL cases treated with ibrutinib and sequenced the entire exome in patients who became resistant (an exome sequence is not as comprehensive as a genome but it is still pretty dang impressive).
In resistant cases, they found that the binding site for ibrutinib on BTK had been mutated in two cases and in a third case, an enzyme downstream of BTK acquired a mutation that turned the protein on.
This is big because it can tell us why patients become resistant to the drug. It is always a good sign that you have hit a very important target when the mechanisms of resistance show how important the pathway actually is. In other words, you know the BCR is important because the CLL cells that become resistant have discovered a way to reactivate the BCR. The next step is figuring out how to get those patients to be sensitive again (perhaps using idelalisib?)
The other significant finding of the paper is that ibrutinib does not result in a bunch of new genetic changes in the same way FCR might.