Chronic Lymphocytic Leukemia: First-Line Treatment Armamentarium


Focused discussion on the first-line treatment armamentarium available to patients diagnosed with chronic lymphocytic leukemia.


Andrew H. Lipsky, MD: As CLL [chronic lymphocytic leukemia] physicians, we’re lucky to have many options for treating patients in the frontline setting, but there are 2 major strategies in use. One is time-limited therapy, which the patient in this case had received initially with venetoclax and obinutuzumab. The other is indefinite therapy with a Bruton tyrosine kinase [BTK] inhibitor, whether that’s a first-generation inhibitor like ibrutinib or a second-generation inhibitor like acalabrutinib or zanubrutinib. When making the choice between an indefinite strategy or a time-limited strategy, it’s a confluence of 3 features that I look at. The first is patient comorbidities, the second is features of the disease, and the third is patient preference. I’m happy to go into that in more detail.

There are certain patient comorbidities that may sway me in 1 direction or another. There are some absolute contraindications to BTK inhibition. For example, for patients receiving therapy with coumadin, that’s an absolute contraindication to a BTK inhibitor. If you can’t get their patient off coumadin, you can’t put them on a BTK inhibitor. Additionally, a history of ventricular arrhythmia might dissuade you from using a BTK inhibitor in the front line. As for comorbidities on the side of time-limited therapy, some patients with time-limited therapy with a high burden of disease are at risk of TLS [tumor lysis syndrome], and comorbidities may make the management of TLS more difficult. Patients with significant chronic kidney disease may not be able to tolerate fluid shifts.

With respect to disease features in the frontline setting, the 1 that’s most salient for me when deciding about a time-limited strategy vs indefinite BTK inhibition is the presence of a TP53 mutation or a deletion 17p. We have relatively robust data that patients with these highest-risk features will have a longer progression-free survival with indefinite inhibition with a BTK inhibitor. I tend to prefer that strategy in these patients.

The third and potentially most important feature is that of patient preference. For many patients in the frontline therapy, I have relative equipoise with respect to selecting time-limited therapy or indefinite strategies. [I talk] to them about how they feel about taking a pill once or twice every day for the rest of their lives, or having a relatively more involved strategy up front that involves the use of IV [intravenous] medications, but doing that only for the first year. [I discuss] how that might impact their life, how that may allow them to continue to do the things that give them the best overall quality of life, and what’s most meaningful for them. Patient preference is definitely a key component.

Transcript edited for clarity.

Related Videos
Related Content