CLL: novel prognostics, and updates on therapy 2

Published on November 30, 2015   35 min

Other Talks in the Therapeutic Area: Haematology

0:04
That section of the talk summarized the current standard of care for initial therapy in both fit and unfit CLL patients. Now I'm going to turn my attention primarily to relapse therapy, but also primarily to the targeted therapies of the B-cell receptor pathway which have been recently approved in CLL and are generating so much excitement. And so in this slide we see a schematic of the B-cell receptor pathway, as well as some of the drugs targeting different proteins in this pathway that have been tested in the last number of years. Some of their early studies tested Dasatinib as a potential LYN inhibitor. And more recently, Dasatinib has also been shown to have activity against BTK. Fostamatinib is a SYk inhibitor and Everolimus is an mTOR inhibitor. And these studies all had fairly modest activity in CLL. Nothing that exciting. The first drugs to generate a huge amount of excitement were Idelalisib, the inhibitor of PI3-kinase delta. And again the delta isoform is most critical in CLL cells. And Ibrutinib, the BTK inhibitor. There have of course, now also been subsequent generations of PI3-kinase and BTK inhibitors that have moved into clinical trials. Listed some of them here. Idelalisib, XL147 which is a pan-PI3-kinase inhibitor that's been tested. IPI 145 is a gamma delta PI3-kinase inhibitor. Gamma's also found in neutrophils and T cells as well as CLL cells. So this may add efficacy but may also add toxicity. That drug is currently in registration trials. And for BTK inhibitors the CC-292 drug has been tested, ONO-4059 has been tested, and now also ACP-196 is moving rapidly into registration trials. I will focus most of my discussion today on Idelalisib and Ibrutinib and then we'll also talk about BCl2 inhibition, as that looks like the next drug to be approved in all likelihood.
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CLL: novel prognostics, and updates on therapy 2

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