Joshua D. Brody, MD, on Follicular Lymphoma: New Data on Epcoritamab, Rituximab, and Lenalidomide

Today we're going to present data about the arm six and seven from the NHL-2 trial. And these are exciting because they are combinations of epcoritamab, a bispecific antibody, with different standards of care for different subsets of lymphoma. So the arm six and arm seven are treating patients in primarily frontline follicular lymphoma, and the arm six trial is combining epcoritamab with a standard of care, rituximab plus Revlimid, lenalidomide. We sometimes call it R-squared. And the arm six is 41 patients with epcoritamab plus R-squared. Primary endpoints here are efficacy. And this was very exciting because R-squared, a standard of care, are very good therapy, but a very imperfect therapy. We have probably less than half of patients, about 48%, in the big RELEVANCE trial from a few years ago with R-squared getting complete remissions. So good, but a lot of room for improvement. And the big punchline of the epcoritamab plus R-squared arm six is that 85% of patients were having complete remissions, quite awesome, and the vast majority of those remissions were ongoing for at least more than 18 months. Median follow up here was about 22 months. So most of these remissions appear to be durable. And again, most patients on the study had complete remissions. And this is despite the fact that these were a standard cohort of patients, about average age for most follicular lymphoma trials, and the majority with advanced stage, the majority with FLIPI scores of two to five. So in this now medium-sized trial, 40 patients, great results and pretty good durability of those remissions. And the safety here looked to be very good. Most of the side effects that we saw were similar to those to R-squared alone. And the epcoritamab-specific side effects that we saw were a couple, primarily cytokine release syndrome. CRS in this trial was completely low-grade, grade one, grade two. About half of patients had CRS, but, again, low-grade and most of those grade one. So other than that, the safety seemed to be similar to R-squared in most ways. There was neutropenia in about 44% of patients, but no febrile neutropenia, the thing we worry most about. And so this is such positive data that we're excited to see further development of this regimen. There are ongoing trials now for epcor plus R-squared in the frontline, a randomized trial, and also for second-line follicular lymphoma patients. And I'll just say a little bit about arm seven of the trial. This is studying maintenance epcoritamab therapy after any standard of care induction, mostly for patients in the first-line. There was a small number of patients in the second-line or beyond, but primarily frontline patients who were in partial or complete remission from whatever their standard of care, R-chemo or otherwise, was. And the exciting result here was that, out of 20 patients, all of the patients who were in a partial remission going to the trial then transferred into complete remission. And these complete remissions, again, for almost all of the patients, appear to be quite durable. Again, median follow up here, just beyond 22 months. So we can use epcoritamab as part of a frontline combination regimen, and we can use it as a maintenance afterwards. And the safety signals, again, low-grade CRS, no patients having grade three or above CRS, and overall grade one CRS in about a third of patients. So, pretty well tolerated, pretty durable remission so far. Another way we can incorporate these novel immunotherapies into or just after frontline therapies.