Metabolic response rates of epcoritamab + R-CHOP in patients with previously untreated (1L) high-risk diffuse large B-cell lymphoma, including double-hit/triple-hit lymphoma: Updated EPCORE NHL-2 data.
Lorenzo Falchi, Michael Roost Clausen, Fritz Offner, Sven de Vos, Joshua Brody, Kim Linton, Sylvia Snauwaert, Raúl Córdoba, Jun Wu, Irina Bykhovski, Liwei Wang, Ali Rana, David Belada
Abstract
7519 Background: Patients (pts) 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 pts with International Prognostic Index (IPI) 3–5 or double-hit/triple-hit lymphoma, representing an underserved pt 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, JCO 2022). Preliminary data for epcoritamab + R-CHOP in 1L DLBCL (NCT04663347) showed encouraging efficacy. Here we present results for a larger cohort with longer follow-up. Methods: Pts with 1L CD20 + DLBCL and IPI ≥3 received subcutaneous epcoritamab (cycle [C] 1–4, QW; C5–6, Q3W) + R-CHOP for 6 Cs (21 d each) followed by epcoritamab monotherapy Q4W (28-d Cs) up to a total of 1 y. Results: As of Oct 31, 2022, 47 pts (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 pts had IPI 3–5, 37 (79%) had stage IV disease, and of 25 pts with FISH data available, 11 (44%) 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 pts; 1 pt 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 (C1D15); all cases resolved. One pt experienced G2 ICANS, which resolved. All response-evaluable pts (100%) had a response, and 76% had a complete metabolic response (CMR; Table). Notably, response rates were similar for double-hit/triple-hit pts (CMR rate, 82% [9/11]). The median durations of response, progression-free survival, and overall survival were not reached. Responses were durable; at 9 mo, an estimated 96% of pts with CMR remained in CMR. Updated data will be presented. Conclusions: Subcutaneous epcoritamab + R-CHOP induces high CMR rates with a manageable safety profile in pts with 1L high-risk DLBCL, including double-hit/triple-hit pts. These results support the ongoing phase 3 study of epcoritamab + R-CHOP in 1L pts (NCT05578976). Clinical trial information: NCT04663347 . [Table: see text]