FDA Approval of Epcoritamab Offers New Hope for R/R Follicular Lymphoma Treatment

Yasmin H. Karimi, MD, assistant professor of medicine at the University of Michigan, explores the significant impact of epcoritamab’s label expansion for relapsed/refractory (R/R) follicular lymphoma following at least 2 lines of therapy. In this interview, she expands on the drug's high response rates and unique bispecific antibody mechanism, offering a well-tolerated treatment option for high-risk patients. Karimi also discusses the potential, though currently limited, role of minimal residual disease (MRD) negativity in guiding treatment decisions for this chronic condition.

This transcript has been lightly edited for clarity.

Transcript

What does epcoritamab’s approval for difficult-to-treat R/R follicular lymphoma mean for this treatment landscape?

Third-line-plus follicular lymphoma has been historically a place where we haven't had...we have some treatment options, but oftentimes the response rates are lower and, especially in difficult-to-treat populations, we tend to see poorer outcomes and shorter duration of responses. For me, seeing the data from the EPCORE-NHL-1 follicular lymphoma cohort—where they enrolled specifically high-risk patients, including patients who were refractory to last line of therapy, patients who had progressed within 24 months of therapy, something that we know is a high-risk feature in follicular lymphoma—and to see an overall response rate of 82% and a CR [complete response] rate of 60% I think is really promising. And I think [it] offers a very well-tolerated, easy-to-administer option for patients who are in this position where they have third-line-plus follicular lymphoma that needs treatment.

Can you explain the mechanism of action of epcoritamab-bysp and what sets it apart from existing R/R follicular lymphoma treatments?

Epcoritamab is a CD20/CD3 bispecific antibody. The way I usually describe it to patients is that there's the CD3 arm that grabs the lymphocytes and then the CD20 arm that grabs the lymphoma cells. And then in close proximity, we see the immune system causing cytotoxic release and the killing of the lymphoma cells. What is unique about epcoritamab is it was designed using something called the DuoBody platform that was an innovative way to design the drug, and it targets an epitope that is a different epitope from what we typically use with our most common CD20 monoclonal antibody, rituximab, so it's a unique epitope that's bound by this.

We do already have one CD20/CD3 bispecific antibody called mosunetuzumab (Lunsumio) that has been approved for follicular lymphoma, and so I think epcoritamab offers us an additional therapy option with a similar class of drugs. We do think that both the mosunetuzumab data as well as the epcoritamab data have shown really promising response rates compared to some of the other targeted therapies that are available in the third-line relapsed/refractory setting.

We can't make cross-trial comparisons to say whether one bispecific is better than the other, that they both have some differences in terms of administration, in terms of both route of administration and duration of therapy. But it's nice to have another option that we can discuss with patients and in our clinics with our patients make a decision about which treatment is right for which patient.

With EPCORE-NHL-1 revealing a correlation between MRD negativity and progression-free survival, how might this relationship influence patient management strategies with epcoritamab?

I think it's probably too early right now to use minimal residual disease to guide treatment and to make treatment decisions for follicular lymphoma. We know follicular lymphoma is a chronic condition; it's treated with palliative intent, so patients are never treated with curative intent.

That being said, we do know in general that patients who have less minimal residual disease or are MRD negative after a certain treatment option tend to have better outcomes, just reflecting that we've done a better job debulking and have less residual tumor volume there. But at this point, I don't think it's going to influence management.

I don't think at this point it's going to tell us when to stop epcoritamab as a therapy that's continued until progression or intolerance. I don't think it's going to tell us when to stop. I don't think it's going to tell us when we need to restart, because follicular lymphoma is also a disease that we know it exists and we know people have it and we can watch it for many, many years with people who have active disease [and] active lymph nodes that are involved, and so all those patients will be MRD positive, and oftentimes we can wait many years before we need to treat them. So, specifically [in] follicular lymphoma, I don't think MRD is going to be something that drives our care.