Abstract Introduction: Epcoritamab (epcor) was the first CD3xCD20 bispecific antibody approved for treatment of R/R DLBCL in May 2023 based on its efficacy and safety in EPCORE NHL-1. Patients (pts) enrolled in clinical trials are highly selected, and those with high-risk features, such as primary refractory disease, early post-CAR T relapse, poor Eastern Cooperative Oncology Group (ECOG) performance status (PS), and CD20+ status are often underrepresented or excluded. As epcor use expands in more heterogeneous, real-world populations, there is increasing interest in understanding pt characteristics and response outcomes associated with its use outside of clinical trials. In particular, pts with DLBCL that is resistant to, or relapse soon after, CAR T are left with limited treatment options and often present with rapidly progressive, resistant disease, making them especially challenging to manage. Generating real-world evidence is critical for informing optimal use of epcor in routine practice. Methods: Real-EPCOR is a multicenter US retrospective chart review study at 8 academic and community oncology centers designed to evaluate the real-world use of epcor. Eligible pts are adults (≥18 years) with R/R DLBCL and ≥2 prior lines of therapy (LOT) who initiated epcor outside of a clinical trial after 5/19/23. Pt demographic, clinical, and treatment data were collected, including ECOG PS, refractory status, prior CAR T, and CD20+ status. Overall response rate (ORR) was evaluated during epcor treatment and defined as the proportion of pts achieving complete response (CR) or partial response among pts with ≥1 evaluable response assessment or who died due to disease progression before response assessment. ORR and CR rate were calculated for the entire cohort, for pts receiving ≥2 cycles of epcor (full cycle is 28 days), and for pts who received prior CAR T. Results: This interim analysis included 34 pts from 2 centers. Data collection and analysis is ongoing and updated results with additional pts and longer follow-up may be included at time of presentation. Median age was 67 years; 68% pts were male and 85% were White. Median time from DLBCL diagnosis to initiation of epcor was 15.5 months. The most common comorbidities were cardiovascular disease (59%) and diabetes mellitus (29%). ECOG PS was ≥2 in 29% of pts, and 85% of pts had Ann Arbor stage 3-4 disease. Nearly all (97%) had CD20+ DLBCL. High-risk features were common at time of epcor initiation, including 53% with International Prognostic Index (IPI) ≥3, 26% with double-hit, and 24% with non-GCB subtype. Among pts who received ≥2 cycles of epcor (n=15), 20% had ECOG PS ≥2 and 33% had IPI ≥3; in post-CAR T pts, 22% had ECOG PS ≥2 and 57% had IPI ≥3. Median number of prior LOT was 3 (range: 2–9); 44% of pts initiated epcor as 3L therapy. Prior to epcor, 41% had primary refractory disease. Following their most recent therapy, 72% had refractory disease, and 43% had DLBCL that was refractory to all prior LOT in those with known refractory status. Most pts (68%) received prior CAR T, with a median interval of 4.6 months from infusion to epcor initiation, and 23% initiated epcor ≤2 months from CAR T. 15 pts (44%) received CAR T in the LOT immediately prior to epcor, 9 (60%) of whom were refractory to CAR T. The ORR was 50% and CR rate was 29% in the overall evaluable population (n=24). 10 pts were not evaluable, as they did not undergo a response assessment either because they remained alive without assessment or experienced a non-progression-related event. Among pts who received ≥2 cycles of epcor, ORR was 85% and CR rate was 54% in the evaluable population (n=13). Among 23 post-CAR T pts, ORR was 53% and CR rate was 33% in the evaluable population (n=15). Conclusion: In this real-world interim analysis, pts with R/R DLBCL treated with epcor had a high proportion of CD20+ disease, higher-risk clinical features, greater comorbidity burden, and more complex treatment histories, including a substantial proportion with prior CAR T, compared to pts in EPCORE NHL-1. Therefore, the ORR remains highly meaningful in the overall cohort despite being lower than the trial. Encouraging ORRs among those who received ≥2 cycles of epcor or had prior CAR T suggest that epcor monotherapy may provide clinical benefit even in difficult-to-treat pts in the real-world setting. Ongoing real-world survival analyses will inform the optimal use of epcor within the evolving treatment landscape of R/R DLBCL.
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