Acalabrutinib in R/R MCL

Transcript: Ian Flinn, MD: What about acalabrutinib? Acalabrutinib also has an indication, in fact its first indication, was in mantle cell lymphoma. The experiences were more widespread than in zanubrutinib, but are you using it a lot?

Tycel Jovelle Phillips, MD: I’m using it patient by patient. Some of the key points of acalabrutinib are, when the first trials came out, less bleeding and less atrial fibrillation. Obviously, as we’ve had more hands-on experience with it, some of the stuff has faltered. You still see some of these things come up.

In essence, if I have a patient with a known cardiac history, I’m more likely to use acalabrutinib than ibrutinib. Again, if I have an issue with patient compliance, it’s the ibrutinib versus acalabrutinib. I’ll be honest, insurance companies will usually dictate what I can prescribe because the co-pays are different. You think, “same class of drug, same co-pay,” but I’ve run into an issue where ibrutinib is a $20 co-pay and acalabrutinib is $1000, and vice versa.

Ian Flinn, MD: That is crazy.

Tycel Jovelle Phillips, MD: Yes. In that situation, that’s dictating for the most, part how we’re choosing this. Again, that’s with the assumption that efficacy is the same and toxicity, other than in a few situations, is probably pretty similar between the 2 drugs. If I have a cardiac patient, I’ll probably try to fight a little bit more, but other than that, it’s really what I can get approved.

Ian Flinn, MD: There is an issue, I think, with acalabrutinib. Most people argue that the efficacy is as good or better. I never heard anybody argue that the efficacy was lower with acalabrutinib, but some people argue that the adverse event [AE] profile is better. I don’t know what’s happening in Florida, but at least in Tennessee, we have a number of patients who are on proton pump inhibitors [PPIs]. While I would like to use acalabrutinib, you can’t.

Bijal Shah, MD: Correct. That is an issue. My sense was, that also was an issue with ibrutinib. I know that there were some data to suggest, no, it’s safe to take ibrutinib even with the proton pump inhibitors, but I was seeing less activity.

Ian Flinn, MD: With ACALA [acalabrutinib], you just don’t absorb it unless you have an acidic stomach, right?

Bijal Shah, MD: Right, exactly. I think zanubrutinib is safe to take with PPIs. Is that correct?

Tycel Jovelle Phillips, MD: I think you’re correct. I don’t remember there being an exclusion in the clinical trials, which has popped up quite a bit, as you mentioned, with ACALA [acalabrutinib].

Ian Flinn, MD: We do have a little bit more data—a longer follow-up, I think—with ACALA [acalabrutinib] than with zanubrutinib. There have been data presented in multiple different formats with 24-month follow-up. The last presentation gave me confidence in that drug.

Bijal Shah, MD: Yes, obviously the overall response rate from the trial when presented was quite high—81%—which, at first glance, looked better than ibrutinib, but with different imaging modalities. With the longer term follow-up, at least at 24 months, you had a duration of responses of 20-plus months in that situation, and PFS [progression-free survival] of at least 19 months. Seventy-two percent of those patients were still in remission at the time of that assessment. Again, long-term responses are durable.

First line, it was a slightly earlier patient population than ibrutinib, but it speaks to the argument that it seems like the earlier we give the BTK [Bruton tyrosine kinase] inhibitors, the better and more durable the responses may be in our patients. Longer-term follow-up is needed as far as revealing more safety data, because even in the 24 months, you start to pick up some more hints of some bleeding and other situations that didn’t come up in the initial assessment. As we get more long-term follow-up and we start approaching the 5-year follow-up that we have with ibrutinib, I’d be quite curious to see what the AE profile looks like at that time.

Ian Flinn, MD: Is there anything else that will guide our decisions? It’s nice to have the embarrassment of riches here, to have 3 different drugs that we can use in this setting that, frankly, all are quite good and a major improvement in our care for mantle cell lymphomas. Javier, do any of the other data convince you? There are data on BTK occupancy. There’s half-life and all these other biological rationales. We can look at the kinematics and 1 is cleaner than the next. Does that matter, or is it only what happens in the patient? Is that the only ultimate test?

Javier Munoz, MD, FACP: Excellent point.

Transcript Edited for Clarity