ERIC CLL 2026 | Addressing changes to genomic prognostic markers in CLL beyond the chemotherapy era

Yeah, we discussed in the biomarker session, we discussed the different biomarkers. Elias also obviously gave a very good summary for the genetic changes, but the bottom line is that TP53 abnormalities and even immunoglobulin locus are still very relevant. The TP53 is the feature that confers high-risk CLL, and the current EHR guidelines advocate continuous therapy for patients with TP53 aberrations. This is not so clear for unmutated patients. But again, we know that mutated CLL responds really very well to single agent fixed duration therapy. So it’s important to know that and to be able to tell patients this is probably the only treatment you ever need. You know, don’t worry about doing complicated stuff on MRD. You have mutated CLL, so this is very good news. Whereas for the unmutated patients, we need to think very carefully about whether an MRD-directed therapy in future will be the way to go. And we don’t know that yet, so we have to do the studies. So in essence, we also discussed, I should say, complex karyotype. Of course, the problem with complex karyotype is that there are many different techniques out there that laboratories are using. Very often, these days, laboratories have very little choice in which technology they’re using. So in my lab in the United Kingdom, we primarily focused on whole genome sequencing. Other labs are using array technology. Of course, the CLL specialists want to use stimulated CLL cells with karyotyping, subsequent karyotyping. They’re very different technologies and they need different cutoffs. And that is really what is preventing us from introducing complex karyotype into the routine biomarker analysis. There’s also a separate issue, which is that a lot of patients with complex karyotype also have TP53 aberrations. So you’re having to go through a tremendous standardization effort for what is ultimately a very small number of people, which are the ones who do not have TP53 aberrations, but still complex karyotype and they are very rare. So the other very small subgroup but still significant group of patients we talked about are the ones that have a stereotyped subset too. The current fifth edition of the WHO guidelines essentially says that this is an essential diagnostic tool that we should be looking for. The numbers of people with this subset are quite small, but there is a rationale for looking out for them because they are usually in the straightforward analysis coming up as mutated, but they have a poorer outcome that is equivalent to unmutated patients. So it does make sense to separate them out. Yeah, so we discussed those details. Bottom line is that at the very least, the TP53 mutation and deletion analysis plus the immunoglobulin analysis for the homology to the germline are the essential tests.

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