ASH Review: Epcoritamab

If there was a Big Winner for Follicular Lymphoma at ASH this year, it was without a doubt Epcoritamab.

Epcoritamab is a bispecific antibody, meaning it has two mechanisms working. On one side, it attaches to a protein on the surface of the cancerous B cell, and then also attaches to a protein on a T cell, an immune cell. In this way a bispecific uses the body's immune system to treat the cancer.

The research that has everyone so excited is the results of a phase 3 clinical trial, also published in the prestigious medical journal The Lancet, as "Epcoritamab, lenalidomide, and rituximab versus lenalidomide and rituximab for relapsed or refractory follicular lymphoma (EPCORE FL-1): a global, open-label, randomised, phase 3 trial."

The results really are pretty exciting. This is a phase 3 randomized trial, which means the researchers split a large group of patients into two, so they could directly compare the results of two different  treatments. This kind of trial is considered the most accurate (rather than comparing one group to the results of a trial that happened a few years ago). In this case, one group was given R-squared (Rituxan + Lenalidomide/Revlimid), while the other was given R-Squared plus Epcoritamab. There were 448 patients in the trial (a pretty large number), and all had relapsed or refractory disease (they had already had treatment, and it didn't work or no longer worked).

With a median follow-up of 14.8 months, the Overall Response rate for the Epcoritamab group was 95% (versus 79% for the R-squared group). The Complete Response Rate was 83% for Epcoritamab and 50% for R-squared. 

The Progression-Free Survival for the Epcoritamab group was higher, with estimated PFS of 16 months in 85.5% of that group versus 40.2% in the R-squared group. (They had to use an estimate because some patients hadn't reached the median time yet.)

With a "triplet" -- a combination of three different treatments -- like this one, safety is always an issue. Three treatments might mean three times the effectiveness, but can also mean three times the side effects or adverse events. Grade 3 (serious) adverse events were higher for the Epcoritamab group (219 of 243, or 90% of that group, versus 161 of 238, or 68% of the R-squared group), which was to be expected. Cytokine Release Syndrome, which can be very dangerous, was low grade for the Epcoritamab group, and was managed by the doctors.

I was going to link to a few videos of Lymphoma experts talking about the results, but they're kind of all the same thing, with the expert repeating the numbers and talking about how exciting this could be (like this one from OncLive). And I do think it's exciting, having finally seen all of the data.

Any skepticism I have comes from whether or not patients will have access to it. It does seem to me that bispecifics are probably more accessible than CAR-T (the two are often talked about together, including by me). CAR-T is great, but more expensive (as one recent bit of research pointed out), which is going to make bispecifics a more popular choice for those who make those decisions about cost. But there are going to be still less expensive options for R/R patients, probably. I hope FL patients can get the best treatment available, no matter the cost.

This isn't the last we're going to hear about Epcoritamab. There were many ASH presentations on this treatment, for many different types of Lymphoma. Two that I thought were interesting were the results of a phase 2 trial of Epcoritamab and Rituxan for untreated FL patients (97% Complete Response Rate in a small trial), and Epcoritamab and R-squared in untreated FL patients (95% Overall Response Rate). 

But it's that randomized, phase 3 trial that really makes me think that Epcoritamab will be around for a while. A large number of patients over a long period of time. It seems pretty likely that it will be a regular part of treatment programs. It might take a while to get to that point, but it probably will.

I'm still looking at ASH abstracts and watching and reading commentaries. I'll have more soon.