FDA Approval of Epcoritamab for Patients With R/R Diffuse Large B-Cell Lymphoma

Tycel Jovelle Phillips, MD, City of Hope, Duarte, California, provides insights into the recent US Food and Drug Administration (FDA) approval of bispecific CD20-directed CD3 T-cell engager epcoritamab-bysp (epcoritamab).

Epcoritamab has been approved as a treatment for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma after ≥2 lines of previous therapy including an anti-CD20 monoclonal antibody therapy.  

Transcript:

Hi, I'm Dr. Tycel Phillips, associate professor at the City of Hope National Medical Center in Duarte, California. I'm here to talk about epcoritamab, which is a recently approved subcutaneous bio-specific antibody that was approved for diffuse large B-cell lymphoma. 

Oncology Learning Network: What is epcoritamab? What data led to this approval?

Epcoritamab is a T-cell-engaging bispecific antibody, with 2 binding epitopes. It binds CD3, which engages a patient's T-cells and then binds to CD20, which will bind to, in this situation, the malignant B-cell—B-cell non-Hodgkin lymphoma, diffuse large B-cell lymphoma—then induce a clinical response in this situation.

Once engaged, it will stimulate the T-cells to produce chemicals to induce a response leading to B-cell death. The approval was based on the study EPCORE™ NHL-1, which is a study that looked at epcoritamab in patients with relapsed/refractory B-cell malignancies, specifically looking into diffuse large B-cell lymphoma. At which point they enrolled, I believe, 158 patients, 147 were valuable with diffuse large B-cell lymphoma and high-grade B-cell lymphoma.

The study, overall, produced an overall response rate of around 60% but with, more importantly, a complete response rate of 38% in this patient population. Then for those who have obtained a complete response, the majority of these patients have had some durability of their immune response with over around 89% of these patients still in remission at the time the initial cutoff for the publication for this study.

What is the safety profile of epcoritamab?

So moving forward, looking at the agent with the approval, the major issue with bispecific antibodies and any T-cell engagement treatment has been cytokine release syndrome (CRS), or [immune effector cell-associated neurotoxicity syndrome] (ICANS). In this situation, the incidences of CRS was around 51%, but the majority of this was grade 1 or grade 2, with very few being grade 3 or 4—around only 2.5% being grade 3.

39% of the patients actually had grade 1, which is important, because that's generally manageable in an outpatient setting without the need for more aggressive treatments, such as tocilizumab or even supplemental oxygen, hydration, things of that nature. As far as ICANS, ICANS was very rare, with only 10 patients reporting ICANS on the study, so much less than what we see with CAR-T, which is another T-cell-directed therapy. 

What is the current treatment landscape for these patients? Do you think that this approval will have an immediate impact in real-world practice?

I think overall, it's very important for our patients, given obviously in the third-line plus setting, there's a lack of options, especially with polatuzumab being moved into a frontline setting. We're not really having much understanding of what that means for the relapsed/refractory setting. Can these patients re-receive polatuzumab? Will they tolerate it? Because we know there's sometimes a limit to how much polatuzumab a patient can receive in their lifetime. 

And thus, we're really left with loncastuximab, which is another CD19-directed therapy, very similar, targeting the same thing that CAR-T does. We don't necessarily know data in CD19 loss with loncastuximab. And then there's lenalidomide and tafasitamab, which unfortunately, the real-world data doesn't necessarily equal what we see in the clinical trials. So these patients do need other options, and epcoritamab is an option that can be given as an off-the-shelf option. 

So, increasing the accessibility of the agent to patients who either can't get access to CAR-T, don't have family support to allow them to get the CAR-T, or they don't want to relocate to get the CAR-T. So they can actually get this, hopefully, locally and closer to where they live.

What advice do you have for practicing oncologists that are interested in using epcoritamab for treatment of their patients? 

I think the biggest thing is obviously being familiar with the drug, being familiar with the timing of CRS, as most of the CRS events occurred on cycle 1, day 15, because epcoritamab does use a step-up dosing. So you get a 0.16 milligram dose on day 1, a 0.8 milligram dose on day 8, and then 48 milligrams on cycle 1, day 15, which is a full dose. And you'll receive 48 milligrams thereafter, weekly, through cycle 3, then every other week from cycles 4 through 9, and then on cycle 10, it's just once a month. Most of the CRS events, as mentioned before, occurred on cycle 1, day 15. You do have some events on cycle 1, day 1. A little bit less on cycle 1, day 8, and then you see very little after cycle 1, day 15. So 62% of the events occurred with cycle 1, day 15, and 92% of the overall, the CRS events, occurred during cycle 1.

So, just being familiar with the timing of it, making sure that your staff is educated, especially in nursing, on-calls at night, on-call nurses, your ER staff, so they can be aware of what to look out for. Because again, with the main event being CRS and the main symptom of CRS being fever, I think the practitioners need to be aware of that, educate patients and staff so that they can manage and treat the CRS, and not focus on what we traditionally would focus on with fever, which is infection.

What are the next steps for investigating epcoritamab in this or other populations? 

I think in this situation, because there's a recommendation of a hospital stay, I think we're going to get further exploration of how epcoritamab performs clinically just as a true outpatient treatment, without the incorporation of a required hospital stay. And then I'm sure as other time comes on, we'll look at epcoritamab, in combination with other treatments, such as chemo-immunotherapy, and also see where epcoritamab can possibly utilize in a second-line setting for those patients who probably qualify for CAR-T but can't get to CAR-T.

Because again, in those situation, we know even though CAR-T has been approved in second and third line, probably on a third of all eligible patients actually make it to CAR-T. So having something in that setting that we can use, in cases where they can't get to CAR-T, will be quite important.

Is there anything else pertaining to this approval or the study findings that you'd like to add?

I think it's an exciting time for patients and practitioners. I mean, to get our hands on this treatment will be, hopefully, quite beneficial. And as we all get more comfortable with using epcoritamab, then used to the side effects, I mean, I think it'll be a boon for our patients. Because even though CAR-T is curative, and if you can get the CAR-T, I think you should get the CAR-T—but the problem with CAR-T, again, is the access, meaning it's limited to a certain site, so it's not in the hands of everyone. 

Whereas, epcoritamab, in this situation, once you get more experience and proper education with utilization of this agent, I think it'll be something that could be implemented in a more diverse patient and practitioner practice, so you're not necessarily isolated to academic centers.

Source:

FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. US Food and Drug Administration; May 19, 2023. Accessed June 28, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell