Fixed-Duration Epcoritamab Is Active, Safe in Older Newly Diagnosed LBCL

Findings from the phase 2 EPCORE DLBCL-3 trial (NCT05660967) showed that fixed-duration subcutaneous epcoritamab-bysp (Epkinly) generated responses and was safe in older patients with newly diagnosed large B-cell lymphoma (LBCL) who were ineligible to receive anthracycline-based therapy. Data were presented at the 2024 ASH Annual Meeting.

Among the full analysis set (n = 45) and patients who were evaluable for response (n = 40), respectively, the objective response rate (ORR) was 69% and 78%, the complete response (CR) rate was 62% and 70%, and the partial response (PR) rate was 7% and 8%. Of 15 patients with a response and evaluable minimal residual disease (MRD) status—including 14 who achieved a CR and 1 with a PR—93% (n =14/15) of patients had MRD-negative status.

With a median duration of treatment of 6.6 months (range, 0.03-12.0) and a median number of 7 treatment cycles (range, 1-12), patients experienced a median time to response (TTR) of 1.5 months (range, 1.2-3.4). Additionally, data showed a median time to CR of 2.5 months (range, 1.2-5.4). Responses deepened from PRs to CRs in 7 patients, and of 9 who finished study treatment, 8 had sustained CRs at the time of data cutoff.

The median follow-up for duration of response (DOR) was 6.4 months (range, 0.03+ to 14.1+), and the median follow-up for duration of CR (DOCR) was 5.4 months (range, 0.03+ to 14.1+). At 6 months, the likelihood of remaining in response and CR was 82% and 84%, respectively. Additionally, 84% (n = 26/31) of responses and 89% (n = 25/28) of CRs were sustained at data cutoff.

At 6 months, epcoritamab yielded a progression-free survival (PFS) rate of 73% and an overall survival (OS) rate of 81%. Neither the median PFS nor OS were reached; the median time for follow-up was 8.1 months (range, 0.03+ to 17.0+) and 9.5 months (range, 0.4-17.7+). Data showed that 9 patients died due to disease progression (n = 6) or adverse effects (AE; n = 3).

“Epcoritamab monotherapy is a promising chemotherapy-free treatment option for older patients with comorbidities and newly diagnosed LBCL who are deemed ineligible for anthracycline-based regimens,” Franck Morschhauser, MD, PhD, a professor of hematology at the University of Lille at CHU Lille in Lille, France, said in the presentation.

In the open-label phase 2 trial, patients with newly diagnosed, CD20-positive LBCL were randomly assigned 1:1 to receive epcoritamab alone or in combination with lenalidomide (Revlimid). In the monotherapy arm, patients received epcoritamab subcutaneously at 48 mg once weekly for cycles 1 to 3 followed by once every 4 weeks on cycles 4 to 12. The data cutoff date was September 21, 2024, and the median follow-up was 9.5 months (range, 0.4 to 17.7+).

The trial’s primary end point was CR rate based on Lugano criteria. Secondary end points included ORR, TTR, DOR, DOCR, PFS, OS, MRD negativity, and safety.

Patients with diffuse LBCL (DLBCL) not otherwise specified, T-cell or histiocyte-rich DLBCL, double-hit or triple-hit DLBCL, or grade 3 follicular lymphoma with an Immune Effector Cell Encephalopathyscore of at least 8 were eligible for enrollment. Other requirements for study entry included having an ECOG performance status of 0 to 2, ineligibility to undergo anthracycline-containing treatment or cytotoxic chemotherapy due to being 80 years or older or 75 years or older with a comorbidity, and measurable disease per CT/MRI.

Investigators screened a total of 120 patients, and 88 underwent randomization. A total of 44 patients received epcoritamab monotherapy, with 9 completing their treatment course and 14 still undergoing therapy at data cutoff.

The median patient age was 81 years (range, 77-95). Of note, 44% of patients were 80 to 85 years old, and 38% were 85 years or older. Additionally, 58% of patients had an International Prognostic Index score of 3 to 5. The most common cardiovascular comorbidities and risk factors included hypertension (78%), elevated cardiac enzymes (71%), atrial fibrillation (16%), and coronary artery disease or prior myocardial infarction (16%). Other data showed that 87% of patients had cardiac and/or cardiovascular disorders, and 40% had other comorbidities that made them unsuitable candidates to receive cytotoxic therapy.

Cytokine release syndrome (CRS) occurred in 71% of patients, with grade 1 events affecting 39%, grade 2 in 27%, and grade 3 events in 5% of patients. The median time to CRS onset following the first full dose was 15 hours (range, 9-26), and the median time to resolution was 2 days (range, 1-5). Investigators noted that 97% of CRS events were reported in cycle 1, with 32% of patients receiving tocilizumab (Actemra).

Immune effector cell-associated neurotoxicity syndrome (ICANS) affected 16% of patients, with 4 experiencing concurrent CRS or capillary leak syndrome. The median time to ICANS onset was 28 days (range, 17-38), with all events resolving at a median time of 2 days (range, 1-22). Treatment was delayed for 11% of patients and discontinued for 2% due to ICANS.

Other toxicities included fatigue, constipation, nausea, and diarrhea. Serious infections occurred in 18% of patients, which included serious COVID-19 infections in 9%. Neutropenia affected 9% of patients, and 18% discontinued treatment due to treatment-emergent AEs (TEAEs). Fatal TEAEs occurred in 5 patients, which included COVID-19 (n = 2), cytomegalovirus reactivation (n = 1), tumor hemorrhage (n = 1), and tumor lysis syndrome (n = 1).

Reference

Morschhauser F, Belada D, Duell J, et al. EPCORE DLBCL-3 first disclosure: fixed-duration epcoritamab monotherapy in older (≥75 y), anthracycline-ineligible patients with previously untreated large b-cell lymphoma. Blood. 2024;144(suppl 1):867. doi:10.1182/blood-2024-199271