Acalabrutinib Treatment Considerations in CLL

Jennifer R. Brown, MD, PhD: I actually think the clinical trial data underestimate the extent to which acalabrutinib is so much better tolerated by patients than ibrutinib. You don’t see much of the general malaise and fatigue that can afflict a significant percentage of patients on ibrutinib. I also haven’t seen any cardiac toxicity, although we do have the ELEVATE CLL TN trial, which demonstrated about a 3.5% to 4% rate of atrial fibrillation compared with 0.5% in the obinutuzumab-chlorambucil arm. But still, with 2½-year follow-up of that trial, you would expect atrial fibrillation with ibrutinib patients to 10% to 15%.

Alan Skarbnik, MD: I agree. My clinical experience is that it’s a much better-tolerated drug. Unfortunately, we have to wait for the head-to-head data to compare more efficiently and statistically. But certainly, my clinical experience is better. One thing I have not seen significantly with acalabrutinib is the joint pain and arthralgias that I see a lot with ibrutinib. That tends to be something that is really dose limiting for those patients.

The most common adverse effect of acalabrutinib tends to be the headache. Fortunately, it’s fairly well controlled with the use of caffeine. I tell my patients to drink coffee in the morning with their acalabrutinib. It’s a twice-a-day pill. It’s given as 100 mg twice a day. This is front loaded. In general, you see that in the first couple of months, and then it tends to go away. You may see a little diarrhea in the beginning as well, but that tends to go away after a couple of months. It’s fairly well tolerated. Again, the only reason to decrease the dose off the bat is the same reason as with ibrutinib. It’s important to remember that the medications can interact with CYP3A4. Particularly, some antihypertensives can interact with CPY3A4. Many times, we forget about those, especially in the older population. Also, it’s important to note that patients should not drink grapefruit products or star fruit or Seville oranges, which no one eats because they are very bitter. But it’s in marmalade. It’s in orange marmalade, so we should stay away from that.

Jennifer R. Brown, MD, PhD: On that note, another important issue with acalabrutinib is that if people are on PPIs [proton pump inhibitors], this does decrease the absorption of acalabrutinib significantly, which is in contrast with ibrutinib or the newer drug zanubrutinib, which is not approved for CLL but did get an approval for mantle cell lymphoma earlier this year.

Alan Skarbnik, MD: Yeah, that is correct. Acalabrutinib requires an acidic environment in the stomach to be absorbed. So in general, we change patients from PPIs to H2 antagonists, but those have to be given spaced out from the acalabrutinib as well. They cannot interact. It’s on the package insert of the drug. As much as patients can take Tums and things like that—a lot of people who are on PPIs are not strictly on them for the right indication. If we can change them to other kinds of antacids that can be taken PRN [as needed], that’s appropriate as well.

Jennifer R. Brown, MD, PhD: I have actually seen patients with arthralgias on acalabrutinib, but it tends to be much more transient and much less dose limiting than with ibrutinib, which is also how I feel about the bleeding. You still see it, but it’s less of a problem. And the GI [gastrointestinal] adverse effects.

Alan Skarbnik, MD: Yes, absolutely.

Transcript edited for clarity.