Role of BTK Inhibitors in Relapsed/Refractory Follicular Lymphoma


A brief review of BTK inhibitor therapy and its potential role within the relapsed/refractory follicular lymphoma treatment landscape.


Matthew A. Lunning, DO, FACP: One of the areas of follicular lymphoma that I was surprised about, since we’re talking about oral therapies, has been the ROSEWOOD trial, which looked at obinutuzumab and zanubrutinib in relapsed/refractory follicular lymphoma. I saw this as a dark horse trial, like something you really didn’t see coming, and then you saw the data and you’re like, “Well, this is very interesting.” Because we had expected that ibrutinib should work, and then it didn’t. But then we come around to zanubrutinib, a next-generation BTK [Bruton tyrosine kinase inhibitor], perhaps a bit easier on the AE [adverse event] profile, and then partnering it with obinutuzumab in a randomized trial, I was taken aback. So it’ll be interesting to see, I know that’s going further into clinical trials, if a BTK can add or fill the gap that it appears that PI3 kinase inhibitors are leaving. I’m not too much of a user of copanlisib right now, just because of its schedule. It reminds me a bit of like romidepsin, where you’re multiple weeks on and it’s IV [intravenous]. In this patient scenario, they’re traveling a distance, it’s a lot to ask to get IV therapy. I don’t know your thoughts on where BTKs may end up in follicular lymphoma, is there going to be room?

Sameh R. Gaballa, MD: I completely share your excitement here. I did not see this coming. We’ve all seen the ibrutinib data in follicular lymphoma. It does work, it’s just that it hasn’t been as exciting as we would have thought. The data with zanubrutinib, although it was a smaller randomized phase 2 study, not a phase 3 study, the PFS [progression-free survival], there’s certainly an advantage there in zanubrutinib. The question will be, are we going to see a more confirmatory trial, a phase 3 trial, to try to tease out that question? That combination, it would make a lot of sense, not just in follicular lymphoma, but also marginal zone lymphoma, where zanubrutinib is approved in the relapsed setting. But combining it with obinutuzumab is certainly a combination of interest there. Yes, the more options we get to fill the gap of PI3 kinase inhibitors, that will be a welcomed change. At this time obviously it’s still not approved. But the data look very interesting from the ROSEWOOD trial, and it’ll be interesting to see.

Transcript edited for clarity.

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