BTK Inhibitors for Elderly Patients With CLL


Jennifer R. Brown, MD, PhD: Say you’ve got a 75-year-old patient who has hypertension and diabetes—a few of your typical comorbidities—and they have an unmutated IGVH. How are you going to choose between a BTK [Bruton tyrosine kinase] inhibitor or venetoclax/obinutuzumab therapy?

Alan Skarbnik, MD: That’s a great question. There are a couple of things that need to be taken into consideration. Of course, for the older patient with unmutated IGHV, we’re not going to give chemoimmunotherapy. For patients who have other comorbidities, we need to understand what the potential risks of starting a particular therapy would be. Between the 2 BTK inhibitors, I tend to use acalabrutinib in the older patient population, because my personal experience is that it is better tolerated. And particularly for the cardiovascular concerns, in patients who have hypertension, if they already have a little bit of CHF [congestive heart failure], I don’t want them to go into atrial fibrillation, which has a 10% to 12% risk in this patient population and decompensates their CHF. So between the 2 BTK inhibitors, I would favor acalabrutinib.

Now, another issue is financial toxicity. These patients tend to be on Medicare. They’re going to be on acalabrutinib or ibrutinib continuously, and there are significant copays. Venetoclax/rituximab is a time-limited therapy. They have the opportunity to take the therapy for a year and perhaps discontinue at a certain point in time. Many times, for patients who are unable to meet their copays, we can get grants from societies like LLS [the Leukemia & Lymphoma Society]. This assistance usually covers a year of the drug, so they’re covered for the duration of the treatment. It is a little bit more cumbersome. The patient has to come in for the ramp-up, but it’s front-loaded. After that, the patients just come in monthly for about 6 months for the rituximab or obinutuzumab that’s used in combination in the front line.

For the older patients who don’t have any other risk factors, if there’s no 17p deletion, no 11q deletion, I tend to favor the time-limited venetoclax. I favor this approach mainly because of cost issues for these patients. Also, we know that some adverse events with BTK inhibitors tend to increase over time, particularly hypertension. If a patient has hypertension off the bat, this may be decompensated by the prolonged use of ibrutinib, particularly after 2 to 3 years of the drug. So I try to prevent that complication by using venetoclax.

But as I said before, it’s a case-by-case basis. There are patients who don’t want to come for the ramp-up, or who don’t want to have infusions. For the time-limited therapy, I would certainly use a monoclonal antibody with the venetoclax. If they want to take a pill and they don’t have issues with the cost, then I usually don’t have a problem giving them a BTK inhibitor. And, as I said, I favor acalabrutinib.

Jennifer R. Brown, MD, PhD: I agree completely. I also use acalabrutinib as my BTK inhibitor. This is my first choice, especially for older patients. I also favor the time-limited venetoclax/rituximab in the relapsed setting, or obinutuzumab in the frontline setting. We should just mention the issues that come up comorbidity-wise. If someone has a significant cardiac history or is on anticoagulation and there’s not a big issue giving them venetoclax, I favor venetoclax. Whereas if someone has renal failure at baseline, then I might be a little more inclined to use the BTK inhibitor. But other than that, there’s a substantial patient preference issue, patient cost issue, as you know.

Transcript edited for clarity.

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