ASCO 2026 | Fixed-duration glofitamab monotherapy in R/R MCL: 3.5-year follow-up data

Yeah, so this abstract that’s going to get presented about glofitamab for relapsed refractory mantle cell lymphoma is really just an update of already previously seen work, but with many more patients than were previously described. In fact, the earliest iteration of this was published in Journal of Clinical Oncology more than a year ago, and the results were very promising. In fact, it was submitted for regulatory approval, and I believe the FDA said we’d like to have a larger number of patients so we can show the safety as optimize the minimization of CRS. So, glofitamab, like every bispecific antibody, has primarily low-grade CRS, but a little bit of high-grade CRS in most settings. But in mantle cell lymphoma, all of the immunotherapies we’ve studied have had more CRS, probably just because mantle cell lymphoma has a greater total tumor burden. Even though you don’t necessarily see a large tumor, there’s lots of extranodal involvement, and that really adds up to lots of tumor cells, which results in lots of cytokine release syndrome, CRS, and a little more high-grade CRS. So the recipe has been really quite significantly modified for glofitamab in mantle cell lymphoma. Specifically, there is more pretreatment with obinutuzumab a week or so before the glofitamab even begins to try to get rid of some of that initial tumor burden. And we are a bit more liberal with the use of dexamethasone and tocilizumab in treating these mantle cell lymphoma patients. And most importantly, this is one setting where we probably have to do these first few doses in the hospital. That’s how these trials have been. 

So with that sort of tweaks to the recipe of just minimizing CRS, we have this more recent cohort of mantle cell lymphoma patients. And a quick punchline is, I would say the results are awesome. I would say they are amongst the highest efficacy numbers we’ve ever seen for relapsed/refractory mantle cell lymphoma. And not a head-to-head comparison to CAR T-cells, which to date have probably been the most potent single agent against mantle cell lymphoma. Not a head-to-head, but if you just look at the complete remission rates, they appear to be as high or higher with glofitamab than with FDA-approved CAR T-cells. And, different targets, CD19 CAR T-cells, but still the efficacy seems to be as good or greater with bispecifics than what we have with CAR T-cells. So it doesn’t mean that one should get rid of the other. In fact, I think the future of this will be finding out how to use both probably for these same patients. But results so far, super exciting for what we’ll see. The safety is not nothing. Again, there is still significant CRS even with the optimization, but again, the vast majority, but it’s just low-grade CRS. And I think that’s because we have a kind of a hair-trigger used tocilizumab and extra dexamethasone for these patients. So overall, it’s pretty doable, but it does require hospitalization. So it’s not nothing. And for what you get, I think it is well paid for, meaning the efficacy, I think, is well worth these slightly higher rates of CRS. So very exciting result that’s going to get presented here at ASCO 2026.

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