SOHO 2023 | TP53-aberrant MCL: challenges and treatment approaches

TP53-aberrant mantle cell, this is a really tough one. I will tell you that there’s two different kinds of TP53-aberrant mantle cell. There’s the very highly proliferative blastoid type, and then there’s the non-proliferative type. I think for the highly proliferative type we’re still trying to figure out our way. I think for those patients, often what I will do is incorporate some chemotherapy, recognizing full well that this is not going to be a curative therapy, but something like an R-CHOP regimen just to cytoreduce before coming in with some more targeted agents. My favorite approach in that situation off-trial is to use a lenalidomide-rituximab combination that has been very powerful in our hands, including in the TP53 mutant patients. But again, you want to get some cytoreduction in place first before moving to that immunotherapeutic approach. When we talk about non-proliferative mantle cell lymphoma, I want to be clear, let me say non blastoid and non-proliferative, we learned from the acalabrutinib-lenalidomide-rituximab trial. This is now bringing lenalidomide, rituximab and acalabrutinib on study for patients with non-blastoid mantle cell. And in spite of P53, these patients were achieving deep remissions. In fact, the two-year overall survival was about 100%, despite the fact that around 20 or 30% of those patients had underlying TP53 aberrations.