ICML 2025 | How the MCL treatment landscape is evolving & approaches to different subgroups of patients

I think the main change that we’re seeing in mantle cell lymphoma over the last couple of years is the movement of BTK inhibition into the first-line treatment and we’ve got now four randomized trials that have reported in this era. The ones that have really changed in practice I think firstly the TRIANGLE study which I think most of us would agree has set a new standard of care for the first-line treatment of young, fit patients with mantle cell lymphoma. And I think there’s two major changes. The first is that the addition of ibrutinib in a time-limited fashion to first-line treatment improves failure-free and overall survival. And the second thing is if you give ibrutinib in this setting you can drop the autologous transplant for the vast majority of patients. So I think pretty much everyone who’s got access to a TRIANGLE approach would recommend that as a standard of care approach for these first-line young fit patients. In older patients we’ve got the ECHO study which is recently reported showing the benefit in terms of progression-free survival of acalabrutinib to bendamustine-rituximab and a trend importantly for an overall survival benefit and I think we do need to see how that pans out in the long run. The third approach is the ENRICH study which is using a completely chemo-free approach and omitting chemo completely just using a doublet approach of rituximab plus BTK inhibitor. So I think as physicians we now have to make these choices for different patients. So I think it’s very clear that if you’re a young patient I think most people recommend TRIANGLE and if you’re a patient say significantly older than 70 with other co-morbidities then probably we’re going to go for an ECHO or BTK plus rituximab approach. There’s a big group of patients in that in the middle who potentially could be fit for either a TRIANGLE or an ECHO approach and I think with those patients it’s largely a decision about whether you consider them fit for high-dose chemotherapy and then it becomes a discussion as to whether they would like a time-limited treatment or an ongoing treatment with BTK. There may be some patients with less proliferative disease and I think the ENRICH study and the Nordic group’s ALTAMIRA study have demonstrated this. That if you have a very low-risk disease in terms of low Ki-67, absence of p53 and no blastoid disease, these patients may actually do very well with the doublet treatment of simply BTK inhibitor plus rituximab. So I think if I had a patient like that, particularly if they’re elderly, I might consider offering them a doublet approach of BTK plus rituximab.

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