P1116: high complete metabolic response rates with epcoritamab + r-chop in previously untreated (1l) patients with high-risk diffuse large b-cell lymphoma, including double/triple-hit: epcore nhl-2 update

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Patients with 1L diffuse large B-cell lymphoma (DLBCL) typically receive rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); however, around 40% relapse. Complete response rates and long-term outcomes are worse for high-risk patients with International Prognostic Index (IPI) 3–5 or double-hit/triple-hit lymphoma, representing an underserved patient population requiring better curative options. Data from the pivotal study of single-agent epcoritamab, a T-cell–engaging bispecific antibody, demonstrated impressive efficacy and a manageable safety profile (Thieblemont et al, J Clin Oncol 2022). Preliminary data for epcoritamab + R-CHOP in 1L DLBCL showed encouraging efficacy. Aims: To present results for a larger cohort with longer follow-up from arm 1 (epcoritamab + R-CHOP in 1L DLBCL) of the ongoing phase 1/2 EPCORE™ NHL-2 trial (NCT04663347). Methods: Patients with 1L CD20+ DLBCL and IPI ≥3 received subcutaneous epcoritamab (cycles 1–4, QW; cycles 5–6, Q3W) + R-CHOP for 6 cycles (21 d each) followed by epcoritamab monotherapy Q4W (28-d cycles) up to a total of 1 y. Informed consent was obtained. Results: As of October 31, 2022, 47 patients (median age, 64 y) had received epcoritamab 48 mg + R-CHOP with a median follow-up of 11.5 mo (range, 0.8–15.5). All patients had IPI 3–5, 37 (79%) had stage IV disease, and 11 (44%) of 25 patients with FISH data available had double-hit/triple-hit DLBCL. Median time from diagnosis to first dose was 28 d (range, 3–423). Median dose intensity for R-CHOP was ≥95%. The most common treatment-emergent AEs (TEAEs) of any grade (G) were neutropenia (64%), anemia (62%), CRS (60%), fatigue (40%), pyrexia (40%), injection-site reactions (38%), and nausea (38%). TEAEs led to epcoritamab discontinuation in 3 patients; 1 patient had a G5 TEAE (COVID-19, unrelated to treatment). CRS was predominantly low grade (57% G1–2, 2% G3) and occurred mostly after the first full dose (cycle 1, day 15); all cases resolved. One patient experienced G2 ICANS, which resolved in 4 d. All response-evaluable patients (100%; 46/46) had a response, and 76% (35/46) had a complete metabolic response (CMR). Notably, response rates were similar for patients with double-hit/triple-hit DLBCL (overall response rate, 100% [11/11]; CMR rate, 82% [9/11]). Median progression-free survival (Figure), overall survival, and duration of response were not reached. Responses were durable; at 9 mo, an estimated 96% of patients with CMR remained in CMR. Updated data will be presented. Summary/Conclusion: Subcutaneous epcoritamab + R-CHOP induces high CMR rates with a manageable safety profile in patients with 1L high-risk DLBCL, including double-hit/triple-hit patients. These results support the ongoing phase 3 study of epcoritamab + R-CHOP in 1L patients (NCT05578976).Keywords: Bispecific, Diffuse large B cell lymphoma, Non-Hodgkin’s lymphoma, Hematological malignancy