EHA 2024 | Considering the optimal treatment strategy for patients with genetically high-risk CLL

So actually, as I changed the title slightly I will talk about therapy of genetically high-risk CLL in general because, what I have when we look at the studies in subgroups of patients with TP53 mutation/deletion 17p receiving continuous treatment with BTK inhibitors, we do see for ibrutinib and acalabrutinib that here the prognosis of patients with these aberrations is not inferior to those without.

So maybe continuous treatment with BTK inhibitor is really a maybe a benefit. However, we won’t know for sure before we have the results from the CLL17 trial, which will also include these high-risk patients.

When we look at, on the other hand, time-limited therapies because, particularly young patients, may still want to have time limited-treatments because they want to have, in a sequence of therapies, more options. Then when we look at CLL14 data, we do see that here PFS and also OS is inferior for patients with TP53 aberration. However, when we look at other combinations, particularly extended ibrutinib/venetoclax combination as done in the MD Anderson trial, we do see that here the prognosis becomes much better. And also we have similar results from a Phase II trial from the German CLL study group, the CLL2-GIVe trial using a triplet combination, adding CD20 antibody, also showing that the PFS looks better there.

So, the conclusion for front-line treatment is that we don’t have randomized data, but within the guidelines, continuous treatment is currently preferred. But it seems when you look at the data that maybe extension of time-limited treatment for two years, for example, or a triplet combination may be a good treatment option in that situation as well.