VIDEO: Expert discusses SHINE, ZUMA-2 trials for mantle cell lymphoma

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I think the one big update which I was happy to see is the SHINE trial. This was a randomized study comparing bendamustine, Rituxan, and ibrutinib versus bendamustine and rituximab. And this trial did meet its primary endpoint in improving progression-free survival. It's the first randomized data we have bringing a BTK inhibitor into the frontline setting. And so I'm not sure that you're gonna see many of us use the bendamustine component, meaning I don't know how much that adds in terms of the magnitude of benefit. I do think it justifies the use of BTK inhibitors frontline with or without rituximab for patients with mantle cell lymphoma. And that is a major, major, major update. We are gonna have a similar study design looking at acalabrutinib and so it will be interesting to see whether they show the same thing. And then there is a trial with zanubrutinib. This trial is set up a little bit differently. This will be bendamustine and rituximab versus just the BTK inhibitors, so zanubrutinib and rituximab. And I think there we'll get the opportunity to see, "Hey does, is what I'm saying accurate?"⁣(Dr Shah laughs) We're actually gonna finally be able to prove it. We had a similar trial performed in CLL. And so in CLL it was bendamustine, Rituxan, ibrutinib versus bendamustine and rituximab. And you can see how therapy and CLL has evolved. We've scrapped the chemotherapy. And we're really focusing on using ibrutinib and rituximab as our frontline approach. We did also get an update of the ZUMA-2 data. This is the longer term follow-up showing that responses appeared durable for a very large percentage of the patients. Now have a plateau in terms of the event-free survival. You know, but particularly for those patients who get a complete remission which is a sizable percentage, I think it was around 60 or 65%, those remissions are really lasting a long time. I don't think they've hit the median yet for those who had a complete remission. And that's amazing to see with longer term follow-up. Now we are learning some things and one of those is that bendamustine in, given shortly before CAR T and I have to go back and look at the trial data, I believe it's within six months of getting CAR T. Those patients did not seem to derive the same benefit with CAR T and so they were more likely either to not respond or progress. But more than that, when you look at the expansion of the CAR T-cells, it really was inhibited even though the bendamustine was months prior to moving down that CAR T-cell immunotherapy path. And so it is gonna force us to think a little bit harder about how we sequence our therapies. And again, it brings me back to that SHINE trial, which is, you know, where I started because that again was a major update from ASH, which is to say that, "Yes, bendamustine, Rituxan, and ibrutinib was better than bendamustine and rituximab." But I don't think you're gonna see a lot of us terribly excited about keeping the bendamustine piece. I think we're gonna use that as our rationale now if we're trying to bring BTK inhibitors frontline into this space. Or quite frequently, we wanna do it for a long time, but I think now we're getting closer to that sort of clinical equipoise of saying, "Yes, this is the right thing to do."