Highlights from the iwCLL conference: B-cell receptor Btk, PI3K and multi-molecular BCR inhibitors

Dr Amy Johnson – The Ohio State University, Columbus, USA

I’m here at iwCLL today, I was a moderator for the session this morning about B-cell receptor signalling. It was the session where they chose oral presentations from the abstracts that were submitted and these abstracts that were chosen were about new therapies mostly. Some of those new therapies were targeting the PI3 kinase pathway; we had several presentations on both clinical and preclinical work with PI3 kinase inhibitors. We had a couple of novel agents that are still in early preclinical studies but it’s good to see that there’s going to be a pipeline of new agents coming through. A lot of us have been involved in the development of idelalisib, ibrutinib and so it’s good to see the next generation molecules coming forward.

For oncologists who are watching, what do you think some of the really key findings were today in the session?

There were some presentations about idelalisib, both as a monotherapy and in combination with other agents, other antibodies. It was good to see the differences between those and if there is in addition to adding combination therapy to idelalisib. Just the idea that there are new things, there are new kinases on the rise and a couple of new targets. There was a presentation about a dual PI3 kinase, PIM kinase molecule and so that’s interesting because we don’t know very much yet about PIM kinase as a target. There is some preclinical data out there pointing to PIM kinase as a target, so some data coming out on that. There was also a presentation about targeting the NF-kappa B pathway using an IKK alpha inhibitor which is a novel target that not a lot of people have been looking at. So this group had been developing brand new compounds right there at their institution that they were able to show the early preclinical studies with.

Were there any clinical trial results presented in that session?

Paula Cramer presented her work, the results from the HELIOS study. That data has been presented a couple of times now but her focus on was on the subtype analysis, looking at specific groups within CLL and who might respond better.

For patients with CLL, what do you think are the most exciting findings for them, things that will give them hope?

I think for CLL patients that are out there right now looking for therapies, they should know that the clinical trials that are coming up and clinical trials that are going on now are very promising. We’ve learned a lot from these kinase directed agents like ibrutinib and idelalisib, I think we’ve learned a lot from those agents and the laboratory researchers are really trying to take what we’ve learned from those agents and put it into new drugs in the pipeline.

What’s in the future for your own research?

My research laboratory mostly studies B-cell receptor signalling pathways and we’ve been doing a lot of the work with ibrutinib. So we’re focussing a lot of our research right now on understanding ibrutinib resistance – why do patients have a response and then relapse. We’ve identified a couple of mutations that are important in patients that have developed resistance and we’re trying to understand the biology of those mutations and find ways to target those patients that have become resistant to ibrutinib.