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Treatment with single-agent pirtobrutinib (Jaypirca), a non-covalent Bruton's tyrosine kinase (BTK) inhibitor, showed encouraging efficacy with a tolerable safety profile in a cohort of heavily pretreated patients with relapsed/refractory follicular lymphoma, according to from the multicohort BRUIN trial presented at the recent American Society of Hematology (ASH) annual meeting.

In this final of four exclusive episodes, 名媛直播 brought together three expert leaders in the field, all from Ohio State University Wexner Medical Center in Columbus -- moderator , is joined by , and -- for a virtual roundtable discussion on the follicular lymphoma results from the phase I/II study. Watch other videos in the series here.

Following is a transcript of their remarks:

Maddocks: Let's move on to our last abstract. So we're going to pivot a little bit from cellular immunotherapies and talk about targeted therapy. So we have abstract Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Relapsed/Refractory Follicular Lymphoma: Results from the Phase I/II BRUIN Study.

So before we discuss this abstract, I think it's pretty interesting. We know that BTK inhibitors have been very effective in many of the B-cell malignancies, particularly mantle cell lymphoma, chronic lymphocytic leukemia. But really a lot of the earlier data in follicular lymphoma wasn't all that promising with BTK inhibitors. I mean, overall response rates really like 20%, 35% maybe. But this was presented this year at ASH, pirtobrutinib, non-covalent BTK inhibitor studied in a large cohort of relapsed/refractory B-cell malignancies, including those not exposed and exposed to prior BTK inhibitor. What's your thoughts on this abstract?

Sawalha: Yeah, I was also pleasantly surprised to see these results. I wasn't honestly expecting them, but the data with pirtobrutinib now and recently also zanubrutinib [Brukinsa] with obinutuzumab [Gazyva] in follicular lymphoma, these data are a little bit different than what we saw initially with ibrutinib [Imbruvica], for example.

It's a small study, 48 patients, they're heavily pretreated, a median of three prior lines. But only 29% of patients received lenalidomide [Revlimid], which I think in clinical practice here, I think a higher percentage of patients who received a median three prior lines probably would be exposed to lenalidomide. I would say a very small number of patients received a bispecific antibody or a prior CAR-T, so less than 10%.

But with those in mind, the response rate was 50%, CR [complete response] rate of 15%. I think this is encouraging. At the same time, it's a crowded space with the bispecifics, the CAR T cells, tazemetostat [Tazverik], lenalidomide, and others. So I think it's very encouraging, but I still think we need to have more data and maybe pirtobrutinib would be, I think it would be a good drug to combine with potentially other active agents, especially given it's very good safety profile.

Bond: Yeah, I think the safety profile is one of the real advantages with pirtobrutinib where it is approved already. And I think that this was, I think a pleasant surprise to see that there's more activity than maybe you'd expect with just how difficult it's been to develop the BTK inhibitors.

And so we saw a 50% overall response rate, and then you did see that while the median progression-free survival was just under 6 months, you did see that at 18 months, roughly one-third of patients, were still progression-free. So there is clearly a pretty wide range in how durable the responses were. But I think just given the tolerability of pirtobrutinib, it's exciting to see that there's another drug that has some activity and could readily be, like Dr. Sawalha said, could readily be combined with other treatments. Or in situations where you have somebody that may have barriers to some of the more intensive treatments like CAR-T, that if it's developed further, still having more options is always a good thing. Particularly since we've lost some of the options that we had previously with some of the drugs that have been withdrawn from the market for follicular lymphoma.

Maddocks: Yeah, I was just going to, actually just thinking, that with now there's actually no PI3K inhibitors indicated in this setting. So potentially, although there are a lot of options, that might create a little bit of space, particularly in those combinations.

Alright, thank you guys so much for this great discussion on follicular lymphoma abstracts out of ASH.

Sawalha: Thank you.

Bond: Yeah, thank you.

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