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ERIC 2020 | Treatment approaches for mutated and unmutated CLL

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Freda Stevenson

Freda Stevenson, MSc, DPhil, FRCPath, FMedSci, University of Southampton, Southampton, UK, discusses the treatment approaches for both types of chronic lymphocytic leukemia (CLL). It is important to identify the CLL subtype in order to choose the correct treatment. Various features can also be identified to help understand how the tumor will respond to treatment. Therapies that target B-cell receptors have a good clinical response but develop treatment resistance. There are other treatment options like venetoclax which targets upregulated BCL-2 molecules. New therapies are targeting both BCL-2 receptors and B-cell receptors as well as other cell surface receptors. This interview took place during the European Research Initiative on CLL (ERIC) International Virtual Meeting 2020.

Transcript (edited for clarity)

It impacts diagnosis dramatically to understand whether the cell of origin is own mutated or unmutated. That’s really critical, I think, and many patients want to know which subset they belong to. So you must give them that information, but it also helps clinicians to consider their approach to the disease. Within mutated CLL, it’s particularly important because there are some cases, which are not so benign, which need treatment within mutated CLL...

It impacts diagnosis dramatically to understand whether the cell of origin is own mutated or unmutated. That’s really critical, I think, and many patients want to know which subset they belong to. So you must give them that information, but it also helps clinicians to consider their approach to the disease. Within mutated CLL, it’s particularly important because there are some cases, which are not so benign, which need treatment within mutated CLL. It’s important to understand which those are.

There are various features of mutated CLL cases, which will help the clinicians to understand how aggressive that disease is likely to be, and also how well it might respond to chemotherapy. For example, mutated CLL seems to respond very well to so-called FCR therapy. In fact, some patients are being cured, “if you’re ever cured of a tumor,” by that approach. It definitely impacts on the therapies that can be given. The therapies that target the B-cell receptor, of course, are being used in unmutated CLL as well, very strongly, and are giving good remission, but resistance will develop and is developing. We need to understand more about those resistance mechanisms. But there is also another therapy, which is developing, which has venetoclax, which targets the upregulated Bcl-2 molecule, which is the anti-apoptotic molecule expressed in CLL. Therapy, now, is targeting both Bcl-2 and the B-cell receptor and other molecules on the cell surface. We’ll wait and see from the clinical trial results, which give the best results for the patients.

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