Subcutaneous epcoritamab + GemOx in patients with relapsed or refractory DLBCL: Updated results from EPCORE NHL-2.
Authors: Brody Joshua D. , Joergensen Judit Meszaros , Belada David , Costello Régis , Trneny Marek , Vitolo Umberto , Lewis David John , Karimi Yasmin , Sureda Anna , Andre Marc , Wahlin Björn E. , Lugtenburg Pieternella , Jiang Yajian , Abbas Aqeel , Song Yaou , Risum Malene , Cordoba Raul 
Published: June 2024

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Background: Gemcitabine + oxaliplatin (GemOx) is commonly used with rituximab to treat relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL); however, outcomes are suboptimal: 33% complete response (CR) rate; 5 mo median progression-free survival (PFS); 10 mo median overall survival (OS; Cazelles et al, Leuk Lymphoma 2021). We report additional efficacy and safety results of epcoritamab + GemOx in difficult-to-treat R/R DLBCL (EPCORE™ NHL-2 phase 1/2 trial, NCT04663347). Methods: Adults with R/R CD20+ DLBCL who failed or were ineligible for autologous stem cell transplant (ASCT) enrolled to receive subcutaneous (SC) epcoritamab (2 step-up doses followed by 48-mg full doses) in 28-d cycles (C): QW, C1–3; Q2W, C4–9; Q4W, C≥10 until unacceptable toxicity or disease progression. GemOx was given Q2W in C1–4. The primary endpoint was overall response rate (ORR) per Lugano criteria. Subgroup analyses by prior treatment (tx) and response were performed. Results: As of Sept 1, 2023, 97 pts with ≥6 mo of follow-up had received epcoritamab 48 mg + GemOx (median follow-up, 9.7 mo). Pts had a median of 2 prior lines of tx (pLOT; range, 1–6); 55% had primary refractory disease, 38% had bulky disease (>6 cm), 30% had prior CAR T, and 9% had prior ASCT. Median age was 72 y, with 34% of pts ≥75 y. A median of 7 cycles of epcoritamab and 4 cycles of GemOx were initiated. At data cutoff, tx was ongoing in 46% of pts. ORR was 78% and CR rate was 55%. Median time to CR was 1.7 mo; median duration of CR was 13.3 mo. Additional efficacy outcomes are shown in the Table. Safety was consistent with previous reports. The most common tx-emergent AEs (TEAEs) of any grade (G) were hematologic AEs (68% thrombocytopenia; 59% neutropenia [6% febrile neutropenia]; 51% anemia) and CRS (51%). CRS was primarily low grade (27% G1, 23% G2), with only 1 pt experiencing G3 CRS; all events resolved and none led to tx discontinuation. ICANS was reported in 3 pts (G1, n=2; G3, n=1); all events resolved, but 1 pt discontinued tx. There were 13 fatal TEAEs; in 3 cases, the contribution of epcoritamab + GemOx could not be ruled out: COVID-19, multiple organ dysfunction syndrome, and small intestinal perforation. Conclusions: These long-term results continue to demonstrate that SC epcoritamab in combination with GemOx leads to deep, durable responses, which translate to high rates of PFS and OS in challenging-to-treat, high-risk pts with R/R DLBCL. CR rates were consistently high across prespecified subgroups. Higher CR rates in pts with 1 vs ≥2 pLOT indicate that earlier use may further improve outcomes. No new safety signals were identified. The benefit-risk profile of this combination supports the combinability of epcoritamab in R/R DLBCL. Clinical trial information: NCT04663347 . [Table: see text]