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

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.

Transcript

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.