Novel analysis of 3-y results from the pivotal EPCORE NHL-1 study: Outcomes in patients (pts) with relapsed/refractory large B-cell lymphoma (R/R LBCL) and complete response (CR) at 2 y with epcoritamab (epcor) monotherapy.

Abstract

7043 Background: Depth and duration of CR correlate with long-term outcomes in LBCL. Epcor is a subcutaneous (SC) CD3xCD20 bispecific antibody approved for the treatment (tx) of pts with DLBCL or high-grade BCL after ≥2 lines of tx (LOT). In the 3-y follow-up from the NHL-1 trial, epcor monotherapy led to durable CRs, with a 36-mo median CR duration (mDOCR), 37-mo median progression-free survival (mPFS), and not reached (NR) median overall survival (mOS) in pts with R/R LBCL who had CR. We report long-term outcomes from a post-hoc analysis of the NHL-1 trial in pts who were in CR 2 y after starting tx, referred to herein as pts in CR at 2 y. Methods: Pts with R/R CD20 + LBCL and ≥2 prior LOT received epcor SC in 28-d cycles (C; 0.16- and 0.8-mg step-up doses in C1; 48-mg full dose thereafter; once weekly [QW], C1–3; Q2W, C4–9; Q4W, C≥10) until progressive disease (PD) or unacceptable toxicity. The primary endpoint was overall response rate. Results: As of the May 3, 2024 data cutoff, 41% (65/157) of pts had CR, of whom 49% (n=32) remained in CR at 2 y. Among the 32 pts in CR at 2 y, median age was 63 y, 47% were male, and 66% were refractory to ≥2 consecutive prior LOT. Pts in CR at 2 y vs pts without CR at 2 y had lower tumor burden at baseline (bulky disease >7 cm 19% vs 34%; LDH 294 vs 501 U/L); pts in CR at 2 y had lower baseline ferritin levels (383 vs 856 µg/L) and similar CAR T exposure (38% vs 39%). At data cutoff, median follow-up for pts in CR at 2 y was 37 mo (range 32−46). All but 1 had a response (CR or partial response) by the 2nd assessment at wk 12. mDOCR was NR, and ~96% of pts remained in CR at 3 y. At the data cutoff, the longest ongoing CR was >43 mo. mPFS and mOS were NR. The overall epcor safety profile in pts in CR at 2 y was consistent with that of the intention-to-treat population. Median tx duration was 35 mo (range 8–43); 81% (26/32) of pts remained on tx at 2 y. 19% (5/26) pts still on tx at 2 y had ≥1 serious infection after 2 y, most commonly pneumonia (n=4). Two pts had a fatal infection (COVID-19 pneumonia, pneumonia) after 2 y. At data cutoff, 19/32 (59%) pts with CR at 2 y were still on tx. One pt discontinued (D/C) due to PD; 12 D/C for reasons other than PD, most commonly adverse events (n=6, including the 2 pts with fatal infections above). In 12 pts who D/C due to reasons other than PD, CR was maintained for a median of 14 mo (range 2−28) after tx D/C. Conclusions: This novel subgroup analysis of pts with R/R LBCL in CR at 2 y after starting epcor highlights long-term disease remission, overall survival, and potential for cure with epcor in some pts. Long-term safety remained manageable. These results underscore the benefits of epcor in the 3L+ setting and may inform personalized tx strategies. Additional data to further characterize pts with R/R LBCL and a prolonged CR with epcor monotherapy will be presented. Clinical trial information: NCT03625037 .