Epcoritamab Plus R-ICE Yields High CR Rates and Improves Transplant Eligibility in R/R DLBCL

Epcoritamab Plus R-ICE in DLBCL |
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The addition of epcoritamab-bysp (Epkinly) to rituximab (Rituxan) ifosfamide, carboplatin, and etoposide (R-ICE) salvage therapy led to high overall (ORR) and complete response (CR) rates in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are eligible for autologous stem cell transplantation (ASCT), including those who experienced disease progression no more than 12 months after receipt of first-line therapy, according to data from arm 10 of the phase 1/2 EPCORE NHL-2 trial (NCT04663347).1

Results presented during the 2025 European Hematology Association Congressshowed that, at a median follow-up of 11 months (range, 6-15), the combination elicited an ORR of 87% in the overall patient population (n = 31), which included a CR rate of 65% and a partial response (PR) rate of 23%.

Among patients who experienced disease progression within 12 months of first-line therapy (n = 20), the ORR and CR rates with epcoritamab plus R-ICE were 85% and 55%, respectively. In those who progressed after 12 months from first-line therapy (n = 11), these respective rates were 91% and 82%. Patients who received 1 prior line of therapy (n = 25) achieved an ORR of 88% and CR rate of 68%. In patients who were treated with more than 1 prior line of therapy (n = 6), these respective rates were 83% and 50%.

The majority of patients (65%) completed treatment with epcoritamab plus R-ICE and proceeded to ASCT. Notably, 5 of the 6 partial responses achieved prior to transplant deepened to CRs after receipt of ASCT. At 6 months, an estimated 81% of CRs were ongoing, 74% of patients were progression free, and all patients were alive.

“The results…continue to show that adding epcoritamab to any regimen of chemoimmunotherapy increases the proportion of patients who respond to treatment and could proceed to ASCT, [which is] still considered a curative approach,” Raul Cordoba, MD, PhD, a cardio-oncologist and head of the Lymphoma Unit at the Fundación Jiménez Díaz University Hospital in Madrid, Spain, stated in a presentation of the data.

Study Background and Design

Approximately half of patients with relapsed/refractory DLBCL are also refractory to salvage chemoimmunotherapy, resulting in limited transplant eligibility and poor outcomes. As such, there is an unmet need for regimens that can increase CR rates, thereby allowing more patients to undergo transplant.

The efficacy and safety of adding epcoritamab, a subcutaneous T-cell engaging bispecific antibody, to R-ICE was evaluated in transplant-eligible patients with relapsed/refractory CD20-positive DLBCL as part of the EPCORE NHL-2 trial; this included those with DLBCL not otherwise specified, double- or triple-hit DLBCL, grade 3B follicular lymphoma, or T-cell/histiocyte DLBCL. Patients were required to be relapsed or refractory to 1 or more prior lines of therapy, be eligible to receive R-ICE and high-dose therapy with ASCT, have an ECOG performance status of 0 to 2, have measurable disease by CT or MRI, and display adequate organ function.

Eligible patients received subcutaneous epcoritamab at a dose of 48 mg along with up to 3 cycles of R-ICE until ASCT or disease progression. The R-ICE regimen included rituximab, intravenous (IV) ifosfamide at 5 g/m² every 24 hours, IV carboplatin with an area under the curve of 5 mg/mL per min, and IV etoposide at 100 mg/m².

Epcoritamab dosing was schedule dependent: it was given weekly during a 21-day cycle for cycles 1 through 4; every 2 weeks of a 28-day cycle for cycles 5 through 9; and every 4 weeks during a 28-day cycle for cycle 10 and beyond.

The study’s primary end point was investigator-assessed ORR per Lugano criteria. Key secondary end points included CR rate, duration of response, duration of CR, progression-free survival, overall survival, minimal residual disease–negativity rate, and safety/tolerability.

Baseline Characteristics and Treatment Discontinuation

Among all enrolled patients (n = 31), the median age was 62 years (range, 39-77). The majority of patients were male (55%), White (71%), had an ECOG performance status of 1 (55%), and had stage III/IV disease (61%). Bulky disease, defined as 7 cm or greater, was present in 41% of patients. Two of 10 patients had double- or triplet-hit disease per central lab, and 48% had primary refractory disease.

The median time from diagnosis to treatment initiation was 10 months (range, 1-75). The median number of prior lines of therapy was 1 (range, 1-3), with 81% of patients having received only 1 prior line, 16% receiving 2 prior lines, and 3% treated with 3 prior lines. Most patients experienced disease progression within 12 months of first-line therapy (65%) vs less than 12 months of first-line therapy (35%), and 55% were refractory to anti-CD20 monoclonal antibodies.

The median number of epcoritamab treatment cycles initiated was 4 (range, 2-14), and the median number of R-ICE treatment cycles initiated was 3 (range, 2-3). A high relative dose intensity was maintained throughout all 3 treatment cycles, at 78% or greater for epcoritamab and 80% or greater for R-ICE.

At the data cutoff date of December 18, 2024, with a median follow-up of 11 months, 10% of patients remained on epcoritamab, and 26% of patients discontinued treatment due to disease progression (19%) or other reasons (6%).

Safety Outcomes

The combination’s overall safety profile was manageable, according to Cordoba. All patients experienced any-grade treatment-emergent adverse effects (AEs), 94% of which were grade 3/4; no grade 5 or higher TEAEs were reported. Serious TEAEs occurred in 58% of patients. TEAEs led to trial drug discontinuation or dose delay in 10% and 74% of patients, respectively. Of these TEAEs, none led to epcoritamab discontinuation, although 71% led to epcoritamab dose delay.

The most common TEAEs included neutropenia (grade 1/2, 3%; grade 3, 0%; grade 4, 84%), thrombocytopenia (10%; 19%; 58%), anemia (13%; 52%; 3%), nausea (52%; 3%; 0%), cytokine release syndrome (CRS; 52%; 0%; 0%), hypokalemia (26%; 3%; 3%); pyrexia (29%; 3%; 0%), and constipation (29%; 0%; 0%).

Infections were reported in 58% of patients, 16% of which were considered serious. Febrile neutropenia occurred and subsequently resolved in 13% of patients. Only 1 patient experienced grade 1 immune effector cell–associated neurotoxicity syndrome, which resolved in 2 days and did not require treatment. No instances of clinical tumor lysis syndrome were observed.

The incidence of any-grade CRS was 52%, comprising grade 1 (42%) and grade 2 (10%) events; no grade 3/4 CRS events were observed. The median time to first CRS onset was 17 days (range 15-42), and 31% of patients experiencing this AE received tocilizumab (Actemra). Most CRS events occurred during cycle 1, with 50% occurring after the first full dose of epcoritamab was administered, and 3% occurring after the second full dose. All 16 CRS events were resolved, with a median time to resolution of 2 days (range, 1-8). No CRS events led to epcoritamab discontinuation.

Disclosures: Cordoba reported serving in a consultancy role for BMS, Kyowa Kirin, Genmab, Kite, Janssen, Takeda AstraZeneca, BeiGene, Gilead, Incyte, Lilly, Johnson &Johnson, and Roche; honoraria from AstraZeneca, BeiGene, Gilead, Incyte, Lilly, Johnson &Johnson, Roche; serving on a speaker’s bureau for Genmab, Kite, Janssen, Takeda, AbbVie, AstraZeneca, Kite, Roche; membership on an entity's Board of Directors or advisory committee for and receiving travel support from AstraZeneca, BeiGene, Gilead, Incyte, Lilly, Johnson & Johnson, and Roche; and research funding from Pfizer.

Reference

Cordoba R, Trneny M, De Vos S, et al. First disclosure of epcoritamab + R-ICE in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) eligible for autologous stem cell transplantation (ASCT): EPCORE NHL-2. Presented at: 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract S245.