Considerations for Cardiovascular Adverse Events Associated With BTK Inhibitors for Patients With CLL

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Javid Moslehi, University of California San Francisco, San Francisco, CA, discussed the cardiovascular risks associated with utilization of BTK inhibitors for patients with chronic lymphocytic leukemia (CLL) and outlined best practices for managing these adverse events.

Transcript:

Hi, my name is Javid Moslehi. I'm a cardiologist who specializes in taking care of cancer patients, so hence I'm a cardio-oncologist. I have practiced at multiple institutions. I was at Dana-Farber, then went to Vanderbilt. More recently I've been at UCSF. I specialize as a cardiologist in the care of cancer patients.

The question that often comes up is: why would a cardiologist be taking care of cancer patients? [It’s because] we've learned over the years that, especially with a lot of new treatments in the cancer space there can be adverse effects on the heart, and these can manifest in different ways.

I am at the Lymphoma, Leukemia & Myeloma [Congress] 2022, talking about BTK inhibitors which are used for [chronic lymphocytic leukemia] (CLL), and the adverse cardiovascular issues that come from these therapies. We have learned over the years that BTK inhibitors, and most of our experience comes with the first drug used, ibrutinib, these patients can have increased risk of developing a number of cardiovascular issues, including arrhythmias. Of the arrhythmias, the most obvious one we see is atrial fibrillation, where you have irregularity of the heart rate, which adds a level of complexity for the care of these patients.

The question becomes when somebody is on ibrutinib getting optimal treatment, and if they have the cardiac arrhythmias, [what do we do for that?] During the course of the [presentation], we went through some of the algorithms we use in cardiology to take care of these patients, including rate control as well as anti-coagulation.

Another question that comes up a lot is where there are multiple BTK inhibitors now in the market. What is the differential effect and are there differences with the cardiac adverse effect, namely atrial fibrillation, with these different drugs? At least clinically, what we're seeing is possibly decreased risk with some of the newer agents—[we’re seeing] decreased cardiac issues, including with acalabrutinib and zanubrutinib.

I also wear a different hat. We have a laboratory invested the mechanisms of toxicities, and at least we've been able to use cell-based and mouse-based models to model these toxicities. From these data we have learned that the effects may be off-target, not due to BTK inhibition. The reason you get atrial fibrillation [may not be] due to BTK inhibition, but rather the off-target effects of the drugs. The [off-target effects of the drugs], of course, are different between the different drugs, ibrutinib, acalabrutinib, and zanubrutinib.

Source:

Moslehi, J. Cardiovascular Adverse Events with BTK Inhibitors. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY.