SOHO 2024 | First-line treatment for MCL and selecting between available options

So for first-line mantle cell lymphoma, I think it’s becoming an area where there’s a lot of options that’s difficult to choose from. There are some themes that are very clear and some themes that are becoming increasingly confusing. One of the themes that I think is very clear is for younger patients that can tolerate high-dose cytarabine, that does seem to be a very effective agent, at least as of right now. There are some studies suggesting that maybe, or at least that are pending, that maybe a BTK inhibitor may help during chemoimmunotherapy with some of these patients. The other thing that is somewhat more, is getting more clear, is a P53 mutant patient may not do as well with chemoimmunotherapy as they would with more novel agents like a BTK inhibitor and venetoclax and a monoclonal antibody. Sometimes those therapies work better in those situations. Sometimes chemoimmunotherapy would still be a reasonable choice. I think that’s an area that’s still under investigation. Generally, which chemotherapy approach to use in other patients I think is a bit of an area where it’s more up to patient and provider, both experience and specifics. So there’s many different options from the TRIANGLE-like approach, utilizing R-CHOP, alternating with R-DHACs with ibrutinib during that induction therapy. There are bendamustine-based regimens for older patients, such as the ECHO study that utilized acalabrutinib with bendamustine. Those BTK inhibitor with bendamustine-rituximab induction therapies have shown PFS benefit, but no clear overall survival advantage. So we’ll have to see with time if they do move into that space. we’re eagerly awaiting the results of EA4181 which will hopefully help us determine if cytarabine with bendamustine, rituximab, and acalabrutinib will be helpful, and then whether or not a BTK inhibitor at all is useful in this space is still unclear. So really the TRIANGLE study that has been the the most beneficial I think for us showing that at least a BTK inhibitor included in the induction phase with some maintenance BTK inhibitor does at least seem equal to utilizing an autologous stem cell transplant and consolidation. And then finally, the EA4151 study, which is nearing enrollment closure, will hopefully help us determine if we can utilize MRD assessments to determine if a high-dose chemotherapy with autologous stem cell rescue consolidation is needed or not.