A key opinion leader highlights alternative treatment options to ibrutinib in the first-line setting for chronic lymphocytic leukemia.
Andrew Zelenetz, MD: Are there alternatives to ibrutinib for the first line? There are. We have 2 head-to-head comparative trials in the relapse/refractory setting of ibrutinib vs acalabrutinib, and very recently presented was zanubrutinib vs ibrutinib. Both trials demonstrate at least equal efficacy of the 2 agents. There might be a hint of actually greater efficacy with zanubrutinib, but the data are way too preliminary to make any informed conclusions. One thing that’s clear is that the cardiovascular risks with both alternative agents, acalabrutinib and zanubrutinib, are lower. We see lower atrial fibrillation and lower hypertension. In a patient with preexisting hypertension, I’d shy away from starting with ibrutinib because patients with preexisting hypertension are at greater risk of having that exacerbated by ibrutinib. We don’t see that as much with acalabrutinib or zanubrutinib, for that matter.
Overall, this is a good patient for a single-agent BTK [Bruton tyrosine kinase] inhibitor. The alternative would be treatment along the CLL [chronic lymphocytic leukemia] 14 approach, with obinutuzumab and venetoclax. The advantage is that it’s a time-limited therapy vs an open-ended therapy. People are very comfortable with BTK inhibitors added as a totally appropriate first-line choice.
Now, BTK inhibitors are associated with different sets of adverse effects. All the approved drugs cause bruising and bleeding, and there’s no major difference in them. They all increase infection risk, and that’s because of their impact on the B-cell function. We see rash and diarrhea with all these agents as well. However, as I said, we see fewer cardiovascular effects with zanubrutinib and acalabrutinib, but we do we see them. You can still get atrial fibrillation with acalabrutinib because it’s not as though you can tell someone we’re going to give you this, and there’s no risk whatsoever.
This transcript has been edited for clarity.
Case: A 77-Year-Old Man With Chronic Lymphocytic Leukemia
Initial Presentation
Clinical Workup
Hem/Onc Workup
Treatment
Subgroup and Toxicity Analyses Favor Zanubrutinib Vs Ibrutinib in CLL
June 10th 2024During a Case-Based Roundtable® event, Lori A. Leslie, MD, discussed subgroup analyses and adverse events from the ALPINE trial of zanubrutinib for a patient with relapsed/refractory chronic lymphocytic leukemia in the second article of a 2-part series.
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