ESH CLL 2026 | Molecular biomarkers and prognostic stratification in CLL

So if we talk about prognostic stratification, understanding prognostic factors as those that help us to predict how the disease will evolve before therapy, I think that the typical prognostic markers that we know for years still are valid because starting therapy did not depend or does not depend on which therapy we give to the patient. So these alterations that we cover in some of these sessions, such as SF3B1, NOTCH1, ATM deletions, for instance, may help us to stratify patients based on this risk to predict time to first treatment. It’s true that if we want to understand how the patient will respond to targeted therapies beyond TP53 and IGH mutational status, our information about the other biomarkers are still limited. But there are some abstracts in different congresses and some also presented here at HCLL that suggest that some of these driver alterations such as NOTCH1 or deletions at CDKN2A and B may also have some prognostic value when patients are treated with targeted therapies. In the last years we have seen a lot of advances in all these next-generation sequencing technologies, these small gene panels that allow us to target all these prognostic markers in a single assay. So I’ve seen that many different hospitals and molecular laboratories are already adopting these NGS panels to characterize CLL, especially for TP53, but we and others have been developing NGS panels that allow us to characterize beyond TP53 also all these additional driver alterations in immunoglobulin mutational status and so on. So I think that with using single NGS approaches, the community can have quite a complete understanding of which are the molecular markers of this disease.

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