IWWM-12 2024 | Novel targets and therapeutics being explored in Waldenström’s macroglobulinemia

So we heard about a lot of novel targets at this meeting. Let me just say there’s novel targets and there’s ones that we know about that we can target. For instance, you know CXCR4. This is a very important mutation. It causes drug resistance. We did, you know, talk about the use of drugs like ulocuplumab that can target CXCR4 and what that means really to improving outcomes with BTK inhibitors which still to this data the only approved therapies for Waldenstrom’s. We talked about new BTK inhibitors, predominantly non-covalent ones but also some covalent ones that are showing some great activity. We heard about tirabrutinib in particular being very effective in Bing-Neel’s syndrome. This is when the disease gets into the CNS space. I think that was very exciting. We heard about new agents being used to target BCL2 like sonrotoclax. But we also heard about degraders, this was an exciting meeting around degraders or PROTACs, as we also call them. We heard about the BeiGene molecule BGB-16673. This is showing some very exciting activity in patients that have failed covalent but also non-covalent BTK inhibitors who have Waldenstrom’s macroglobulinemia. I got very excited also about some new targets like HCK. This is actually a molecule that’s upregulated by mutated MYD88. At this meeting we heard about PROTACs that specifically target HCK and are showing really some very impressive preclinical findings. So as time goes on I think PROTACs is going to become more and more important and there are other targets we’re going to be hearing very shortly about the IRAK molecules also being very important and how PROTACs can target them. But this was a great meeting to hear about a lot of new drug development.