ASH 2024 | The impact of BTKis on the treatment landscape for R/R MCL

So for relapsed/refractory mantle cell lymphoma, actually a BTK inhibitor has been the cornerstone of treatment. So if a patient receives frontline immunochemotherapy with or without transplant, depending on their age and fitness, if after years they are disease-relapsed, in today’s practice, a preferred treatment is using a BTK inhibitor. This is regardless of disease risk. Of course, the high-risk patients at the time of relapse, they may derive less benefit from BTK inhibitors. So the treatment of these patients remains challenging. But stay on the track of BTK inhibitors. We now do have a number of non-covalent BTK inhibitors. So if we use covalent BTK inhibitors first, which is the standard care today, like zanubrutinib or acalabrutinib, if there is disease progress, we can move on to use non-covalent BTK inhibitors like pirtobrutinib, which is approved in this setting. So we continue to navigate the BTK targeting in relapsed mantle cell lymphoma. Now in terms of high-risk patients at relapse, we now do have the option of using CAR T-cell therapy for them. Most patients, we probably can do BTK inhibitor in the second line and then reserve CAR-T for the third line. But for high-risk patients, I think there’s an opportunity where we can use BTK inhibitor just for a short duration of time to induce the response and then move on to CAR-T quickly. So it’s sort of using BTK as a debulking and bridging option so that we can get to definitive therapy sooner. And also for high-risk patients, we are using BTK inhibitor treatment as a kind of a backbone and building upon that to explore new combination therapies or using BTK inhibitor to bridge into other therapies like bispecific antibodies that are coming in the pipeline. So as of today, BTK inhibitor again is a cornerstone of treatment for relapsed mantle cell lymphoma. That being said, we do see increasing activity trying to move BTK inhibitors to the frontline therapy of mantle cell lymphoma. So if we use BTK inhibitor in a fixed duration therapy in the frontline, I think there’s still an opportunity of using BTK targeting strategy in a relapse setting. Now the question becomes if a patient is being able to continuously either alone or in combination with chemotherapy for short duration initially, when they relapse, how do we treat those patients? I think the landscape is going to change in the next few years, but good thing is that again we still have combination strategies, we have CAR-T, we have bispecifics, we have many other encouraging and exciting opportunities coming.

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