Background: Epcoritamab induces high complete response (CR) and MRD-negativity rates with manageable safety in patients (pts) with challenging-to-treat R/R LBCL as shown in the pivotal phase 2 study (NCT03625037). Here we present long-term data, an additional efficacy analysis from the expansion cohort, and data from the cycle 1 optimization (C1 OPT) part. Methods: Adults with R/R CD20⁺ LBCL and ≥2 prior systemic therapies received subcutaneous epcoritamab (2 step-up doses, then 48-mg full doses per label) in 28-d Cs. The primary endpoint of the expansion cohort was IRC-assessed overall response rate (ORR). A subgroup analysis evaluated efficacy outcomes by investigator assessment in complete responders with longer follow-up. C1 OPT assessed CRS incidence and severity with hydration and dexamethasone prophylaxis in C1; hospitalization was not required. Results: Overall, 157 LBCL pts were treated in the expansion cohort; 148 had diffuse LBCL (DLBCL) or high-grade B-cell lymphoma (HGBCL). Baseline characteristics were previously reported. As of April 21, 2023, the median follow-up for LBCL was 25.1 mo (range, 0.3+ to 32.7); ORR/CR rates were 63/40% (LBCL) and 61/39% (DLBCL + HGBCL) by IRC. In a subgroup analysis of complete responders with longer follow-up (median, 31.3 mo), median duration of CR was not reached; efficacy outcomes for complete responders are shown in the Table. Long-term safety was consistent with previous reports. CRS remained the most common AE (51% all grade [G]; 32% G1, 16% G2, 3% G3). In C1 OPT, 36 pts were evaluable for CRS with a median follow-up of 1.7 mo. Overall CRS incidence was 22% and events were low grade (14% G1, 8% G2), mostly occurring following the first full dose. All CRS events resolved; none led to treatment discontinuation. Among 60 total pts in C1 OPT, 1 pt experienced ICANS (G1). Additionally, IL-6 levels were lower with C1 OPT and consistent with the observed lower rate and severity of CRS. Preliminary C1 OPT efficacy data were comparable to data observed in the expansion cohort. Conclusions: Epcoritamab monotherapy continues to demonstrate deep and durable responses, with most complete responders remaining in CR and without new safety signals in these long-term follow-up analyses. Implementing simple measures of adequate hydration and prophylactic dexamethasone in C1 markedly reduced the overall incidence and severity of CRS with no impact on efficacy. The continued benefit beyond 2.5 y underlines the long-term efficacy and value of epcoritamab in R/R LBCL. Clinical trial information: NCT03625037.

Data cutoff: October 16, 2023. Median follow-up, 31.3 mo. Per investigator assessment. Kaplan–Meier estimates. Medians were not reached (data not shown). NA, not assessed.