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iwCLL 2025 | A real-world analysis of CNS involvement in CLL
Jacob Soumerai, MD, Massachusetts General Hospital, Boston, MA, comments on the rarity of central nervous system (CNS) involvement in chronic lymphocytic leukemia (CLL), noting that it has an incidence of as low as 0.5 to 1%. Dr Soumerai emphasizes that CNS involvement can occur in both patients with treatment-naive and relapsed/refractory disease, and that novel agents appear to be active and efficacious in this patient population. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2025 in Krakow, Poland.
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Transcript
CNS involvement is very rare in patients with CLL. Depending on the series that you’re looking at, we see this in as little as 0.5 to 1% of patients over a very long period of time. Interestingly, there were actually two presentations on CNS involvement in CLL at this iwCLL meeting. And in both, it again highlighted that novel agents are being used in this setting, that they do appear to be quite active in patients with CNS involvement...
CNS involvement is very rare in patients with CLL. Depending on the series that you’re looking at, we see this in as little as 0.5 to 1% of patients over a very long period of time. Interestingly, there were actually two presentations on CNS involvement in CLL at this iwCLL meeting. And in both, it again highlighted that novel agents are being used in this setting, that they do appear to be quite active in patients with CNS involvement. And also that unexpectedly that we oftentimes see CNS involvement present in folks who have treatment-naive disease, who have not received prior therapies, and so this is not simply something that you need to be thinking about in a more highly refractory, multiply-treated patient. If somebody has CLL and they have any symptoms suggestive of CNS involvement, in particular in our series, they were all patients with leptomeningeal disease, this should really prompt evaluation.
One of the things that was demonstrated both in the other series that was presented, the ERIC consortium, and also in our single-center retrospective series, was that patients who received BTK inhibitor-based strategies seemed to fare better in the ERIC consortium and had favorable outcomes as well in our series. And so from this series, I would say that it’s A, important to remember that this does exist, it’s something you should look for if somebody has symptoms that suggest central nervous system involvement. B, that if you’re looking for an initial line of therapy, that a covalent BTK inhibitor-based strategy is likely a preferred option in these patients. But also that we do have alternative targeted agents that appear, active in our series, for example, we observed some evidence of activity with venetoclax-based therapies, with liso-cel, which I think we would all potentially expect based on what we know of its activity in other lymphoid malignancies with CNS involvement. And so we can reach for some of these targeted therapies in this setting.
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