EHA 2025 | The most important genetic or molecular markers to consider at relapse in patients with CLL

When I have a relapsed patient I usually have a look at the mutation. There are two for me to look at the mutations in two different ways. I look at the somatic mutations that are non-BTK mutations, like the development of TP53, for example. These are higher-risk patients, and on the other hand, I also look at the BTK mutations that are developed, especially if the patient was on a BTK covalent or non-covalent inhibitor. For example, having mutations that are now emerging and we are seeing more with the non-covalent, like the T474 mutation or the domain-dead mutations, like the 528 or the 428 mutations. These mutations do inform me. For example, if a patient, I will be placing my patients on a BTK degrader because we have data showing or other novel therapies, because the old approved medications that we have right now, they are not, they did not show efficacy against those mutations. So I always take the clinical trial route for those patients. These are the important mutations that I look for for my BTK-treated patients. Also, if the patient had any of the BCL2-related mutations that also make me think about taking the BTK degrader route. So looking at those mutations, BTK and non-BTK are very informative right now and they will grow an even bigger role as we grow more information about those emerging mutations. So it’s definitely something that I look at when deciding on the next line of therapy for my patients.

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