Dr Jennifer Brown Speaks on Use of BTK, BCL-2 Inhibitors in CLL Treatment


Jennifer Brown, MD, PhD, Dana-Farber Cancer Institute, shared her thoughts on the current research regarding Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL-2) inhibitors in chronic lymphocytic leukemia (CLL) and what providers should keep in mind before prescribing them.

Jennifer Brown, MD, PhD, director of the Chronic Lymphocytic Leukemia Center and an institute physician at Dana-Farber Cancer Institute, gave insight into provider considerations for prescribing Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL-2) inhibitors to patients with chronic lymphocytic leukemia (CLL) at the annual meeting of the European Hematology Association in Frankfurt, Germany.


In CLL, we are seeing the use of second-generation BTK inhibitors, use of BTK inhibition alongside BCL-2 inhibitors, and studies of third-generation BTK inhibitors. What are the key considerations for clinicians in selecting a therapeutic approach?

Right now, in the frontline setting in the United States, it's really primarily continuous BTK inhibition with a second-generation inhibitor, essentially acalabrutinib or zanubrutinib, vs time-limited therapy with venetoclax/obinutuzumab. We don't have approval yet for BTK or BCL-2 [inhibitors], and the data really showed pretty similar progression-free survival for BTK/BCL-2 as for venetoclax/obinutuzumab. So I think, at present, it's really quite reasonable to stick with venetoclax/obinutuzumab as a time-limited regimen.

For patients with p53 aberration, we do favor [a] continuous BTK inhibitor. And for patients with mutated favorable risk IGHV [immunogloblulin heavy chain], I certainly favor time-limited therapy because they have a good likelihood of achieving undetectable MRD [minimal residual disease] and then a very prolonged remission off therapy.

For all the patients in between, it's something of a long discussion—taking into account their particular risk factors, their goals, and desires. For example, often young patients are happy to come in a lot, do the extra work of a time-limited regimen where sometimes the older patients, they don't want to do that, they just want to go on a BTK inhibitor and more or less be done with their monitoring. And so all of these factors come into play. It's a lengthy discussion with the patient, really.

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