In the second article of a 2-part series, Sameer A. Parikh, MBBS, looks at the risk of cardiac related toxicities with zanubrutinib for patients with relapsed chronic lymphocytic leukemia.
CASE SUMMARY
History and Presentation:
A 70-year-old White man with asymptomatic lymphocytosis identified 4 years previously
Comorbidities:
Medications:
Current Status:
Six Months Later:
Diagnostic Workup:
Due to progression of disease after BCL2 inhibitor, the decision was made to initiate therapy with a Bruton tyrosine kinase (BTK) inhibitor.
Targeted Oncology: What toxicities associated with zanubrutinib (Brukinsa) should other physicians know about? How do these compare with those associated with ibrutinib (Imbruvica)?
SAMEER A. PARIKH, MBBS: The risk of high blood pressure [on zanubrutinib] was lower than with ibrutinib, but the risk of neutropenia was higher with zanubrutinib than ibrutinib.1 However, cough, pneumonia and other infection-related complications were lower [with zanubrutinib]. In general, if you look at the cardiac safety data, the risk was significantly lower with zanubrutinib compared with ibrutnib, which, in my opinion, is why we gravitated toward... zanubrutinib compared with the traditional ibrutinib.
The one thing that wasn’t very different was the risk of hypertension and again, it’s unclear to me why that is the case. I always thought that with atrial fibrillation the risk is based on many other risk factors including hypertension, but apparently, at least in the ALPINE trial [NCT03734016], the risk of hypertension wasn’t lower. The risk of infection was lower in zanubrutinib, despite having a higher risk of neutropenia. That suggests that maybe there are other reasons for these infections.1
How do you address atrial fibrillation (AFib) for patients on a BTK inhibitor?
AFib is usually an early event [when a patient is on a BTK inhibitor therapy], so if you look at the risk of AFib [on zanubrutinib] it happens in the first 12 to 18 months and then [the risk slowly goes down].1 I think if someone does develop AFib beyond that time period, then I would question if I need to do anything different because by that time a lot of patients have had a very good response to the treatment already. I might not change anything if their disease is decently controlled.
Does the risk of hypertension impact your treatment decision?
I’m not going to stop prescribing them anything because I’m worried about hypertension. [When you] look at BTK inhibitors vs non-BTK inhibitors there’s always a high risk of hypertension.2 So, this will induce hypertension, but the question is, is that going to matter to the patient? Because if their hypertension is defined as 140 over 90 [mm Hg], but you’re going to continuously give the BTK inhibitor for 5 to 7 years, [ultimately, the risk is limited over time].
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