Epcoritamab Elicits Durable CR Rates, Increases MRD Negativity in Relapsed/Refractory DLBCL

Of the FDA-approved bispecific antibodies for patients with relapsed/refractory large B-cell lymphoma (LBCL), including diffuse LBCL (DLBCL) and follicular lymphoma, epcoritamab (Epkinly) produced the longest reported median duration of complete response (DOCR) to date, according to 3-year follow-up results from the phase 1/2 EPCORE NHL-1 trial (NCT03625037).1

“The patients who maintained [treatment with epcoritamab] continued to increase their MRD-negativity over time,” Julie M. Vose, MD, MBA, stated during an interview with OncLive® about the trial. “The bottom line is that [epcoritamab] doesn't benefit all patients. However, for those patients who do experience a good response to [epcoritamab], it can be very durable, and a high percentage of patients can become MRD-negative.”

The overall median DOCR with epcoritamab was 36.1 months (95% CI, 20.2–not reached). In patients with LBCL (n = 157), the overall response rate (ORR) was 59%, with a CR rate of 41% and a partial response rate of 17%; in those with DLBCL transformed from follicular lymphoma (n = 32), these rates were 50%, 44%, and 6%. The median duration of response was 20.8% (95% CI, 13.0-32.0) in patients with LBCL and NR (95% CI, 10.6–NR) in patients with DLBCL transformed from follicular lymphoma; the respective 36-month estimates were 39% and 55%.

In the interview, Vose discussed long-term findings from the EPCORE NHL-1 trial, the safety profile of epcoritamab, and the optimal patient characteristics for epcoritamab selection.

Vose serves as a professor and chief of the Division of Oncology and Hematology as well as the George and Peggy Payne Distinguished Chair of Oncology at the University of Nebraska Medical Center/Nebraska Medicine.

OncLive: What updated efficacy findings from the phase 2 EPCORE NHL-1 trial were reported at the 2024 ASH Annual Meeting?

[The trial enrolled] adult patients with high-DLBCL and grade IIIb follicular lymphoma, who had progressed on at least 2 lines of prior therapy, and were treated with subcutaneous epcoritamab in a typical step-up dosing fashion for 28-day cycles. In this study, 157 patients were included. The median age was 64 years, and patients had received a median of 3 prior therapies [range, 2-11]. A high percentage of patients [61%] had primary refractory disease, which is very difficult to manage for this patient population. ORR and CR rates were 59% and 41%, respectively.

The median follow-up time was [approximately] 37 months. The median overall survival [OS] was 18.5 months, and the median progression-free survival for all patients was 4.2 months. [Among] the complete responders, however, it was 37.3 months. This was [emblematic of a] pattern that we're seeing in clinical practice, where patients who don't respond [to epcoritamab] leave the study pretty early, and patients that do respond [are able to stay] on treatment for quite a long time.

At 36 months, an estimated 63% of complete responders [with LBCL] remained alive. [A total of] 119 MRD-evaluable patients were evaluated, and 45% were found to be MRD-negative. As patients [continued on the study], subsequent MRD tests were performed at various time points. There was a landmark analysis performed on day 1 of cycle 3, [which showed that the] 36-month PFS rate was 52% and the OS rate was 55% in all MRD-negative patients. A very small percentage of [MRD-evaluable] patients [were included in] an exploratory analysis. At day 1 of cycle 13, 98% of these patients were MRD-negative. [Overall], although [epcoritamab] doesn't benefit all patients, those who responded to therapy and became MRD-negative did have a good response.

What were some of the safety considerations for epcoritamab to emerge from this study?

The toxicity profile [of epcoritamab] was the same as what has been described previously. [This includes] a low rate of cytokine release syndrome [CRS] that typically [occurs at] day 15 of cycle 1, which is the first full dose. That was low with respect to [the rate of] high-grade CRS. [Immune effector cell-associated neurotoxicity (ICANS)] was very low. Typically, after cycle 1, there's minimal CRS or neurotoxicity. One concern is the potential for infections, [because] these are very heavily pretreated patients with lymphocyte depletion, so patients [need to be monitored] very carefully. The bottom line is that [epcoritamab] doesn't benefit all patients. However, for those patients who do experience a good response to [epcoritamab], it can be very durable, and a high percentage of patients can become MRD-negative.

In which patients would you more strongly consider treatment with epcoritamab?

This would be an option for patients who [were unable to continue] standard induction therapy. This is a good option for patients who are not eligible for more intense regimens, such as autologous transplant or CAR T-cell therapy. It's potentially an outpatient regimen, and once patients get through the first cycle, it's tolerated quite well. One downside is that epcoritamab [requires] frequent dosing, so this may not be a good option for patients who do have to travel a long way, but it [is associated with] very high response rates and acceptable toxicity. Therefore, it's [a viable option for] a large patient population.

Reference

Vose JM, Cheah CY, Clausen MR, et al. 3-year update from the EPCORE NHL-1 Trial: Epcoritamab leads to deep and durable responses in relapsed or refractory large B-cell lymphoma. Blood. 2024;144(suppl 1): 4480. doi: 10.1182/blood-2024-198714