Yu, Junhua

Background: Epcoritamab (epcor) is a first-in-class CD3xCD20 bispecific antibody (bsAb) approved for the treatment of 3L+ LBCL and follicular lymphoma. In the single-arm, phase 1/2, EPCORE NHL-1 trial (NCT03625037), epcor given until disease progression or unacceptable toxicity, demonstrated deep and durable responses, a median overall survival (OS) of 18.5 months, and a manageable safety profile in R/R LBCL. A second CD3xCD20 bsAb given as fixed-treatment duration, glofitamab (glofit), also demonstrated durable responses, conferring a median OS of 11.5 months in the pivotal study. Understanding how long-term outcomes compare among bsAb agents remains an important knowledge gap. With over 2 years of follow-up, in the absence of a head-to-head study, it is now relevant to compare the efficacy of these agents via indirect comparison. This study evaluated OS, progression-free survival (PFS), and duration of complete response (DoCR) of epcor vs glofit in R/R LBCL using data from the respective pivotal trials. Methods: Two analyses were conducted to compare the efficacy of epcor and glofit. First, a matching-adjusted indirect treatment comparison (MAIC) was conducted using published OS and PFS data from the full cohort of the glofit pivotal trial (12.6 months of follow-up, Dickinson et al, 2022) and the epcor pivotal trial (EPCORE NHL-1). Piece-wise hazard ratios (HRs) were calculated when proportional hazards assumptions were not met. Baseline characteristic prognostic variables were selected based on literature, clinical judgement, and empirical statistical testing and were adjusted between epcor and glofit cohorts. Second, in sensitivity analyses, indirect comparisons were conducted using an updated analysis of glofit with longer follow-up that included DoCR, together with OS and PFS data starting at cycle (C) 3 with 32 months of follow-up (Hutchings et al, ASH 2023). Sensitivity analyses with longer follow-up could not be adjusted because glofit pt baseline characteristics were not presented. Aggregate OS and PFS curves for glofit were derived from subgroups of pts with complete response/partial response/no response (CR/PR/NR) at C3 (Hutchings et al, ASH 2023). Aggregate epcor OS and PFS curves were similarly derived for pts with CR/PR/NR at C3 without prior disease progression. Weighted Cox proportional-hazards models were used to estimate the OS and PFS HRs between the 2 comparators. The DoCR comparison included all glofit and epcor pts achieving CR. All comparisons used EPCORE NHL-1 data with a median of 37.1 months of follow-up. Results: Pts enrolled into the pivotal trials of epcor and glofit were comparable by several key baseline characteristics before adjustment: age ≥65 y; male gender; Ann Arbor disease stage III-IV; primary refractory disease; refractory to most recent anti-CD20 therapy; previous chimeric antigen receptor T-cell therapy (CAR T); refractory to CAR T; and previous autologous stem cell transplant (ASCT). MAIC analysis revealed no significant difference in OS benefit from C1 until month 6 (HR 1.08, 95% CI 0.71, 1.64; P=0.72), but a demonstrable OS advantage from 6 months onward (HR 0.60, 95% CI 0.37, 0.98; P=0.04) in favor of epcor. An OS comparison starting at C3 with longer glofit follow-up demonstrated a consistent survival advantage in favor of epcor (HR 0.68, 95% CI 0.46, 1.01; P=0.05). The proportion of pts who received CAR T or ASCT subsequent therapy were similar for epcor and glofit (CAR T: 7.0% vs 8.9%; ASCT: 6.4% vs 6.3%) (National Institute for Health and Care Excellence Glofit Single Technology Appraisal, 2023). The MAIC analysis showed comparable PFS between epcor and glofit (HR 1.06, 95% CI 0.79, 1.41; P=0.71), although there was substantial censoring in the glofit PFS curve due to immature follow-up. With longer follow-up in the analysis starting at C3, with less censoring, the glofit PFS curve remained similar to the epcor PFS curve from C3 until month 6 (HR 0.67, 95% CI 0.42, 1.07; P=0.10), where separation of the PFS curves were observed favoring epcor (HR 0.56, 95% CI 0.33, 0.97; P=0.04). Median DoCR was longer for epcor (36.1 months) vs glofit (26.9 months). Conclusion: These indirect treatment comparisons suggest that epcor may provide an overall survival benefit over glofit through longer PFS with more mature follow-up, potentially driven by longer DoCR. Survival data with longer follow-up in the full glofit cohort are needed to confirm these findings.

e19530 Background: In large B-cell lymphoma (LBCL) trials, racial and ethnic representation is difficult to determine due to underreporting in some regions, or because some patients may not provide data. It is difficult to understand the full extent of any underrepresentation of specific races or ethnicities in these trials relative to the prevalence of LBCL in clinical practice. The objective of this study was to characterize racial and ethnic representation in LBCL real-world databases and recently published LBCL studies. Methods: Analyses of the distribution of different racial and ethnic categories were conducted across 6 real-world clinical practice databases from the United States (US): SEER-Medicare, COTA, Medicare, Optum Market Clarity, Optum CDM, and ConcertAI RWD. In addition, a targeted review of recently published studies in patients with LBCL was conducted to identify reported race and ethnicity distributions. Distributions were described using counts and percentages for each race (Asian, Black, White, and other/unknown/not reported) and ethnicity (Hispanic, non-Hispanic, and other/unknown/not reported) category. Results: Patients with LBCL from the databases included: COTA (N=5848), SEER-Medicare (N=102,548), Medicare (N=136,466), Optum Market Clarity (N=19,649), Optum CDM (N=22,175), and ConcertAI (N=1828). Race and ethnicity distributions are reported in the table. Across databases, Asian (2–6%) and Black (5–8%) races were substantially lower than White race (69–88%). Across various lines of therapy, distributions were similar: 3–5% Asian, 3–5% Black, and 78–82% White. Hispanic ethnicity (5–22%) was substantially lower than non-Hispanic ethnicity (70–91%). In the targeted review, 14 publications of LBCL therapies were identified; of these, 10 did not report racial/ethnic composition. In 4 publications (Salles et al, 2020; Sehn et al, 2020; Bannerji et al, 2022; and a real-world study by Shenoy et al, 2011), Asian, Black, White, and other/unknown/not reported represented 2–13%, 0–7%, 71–89%, and 1–11%, respectively. Conclusions: Information on racial and ethnic distributions in LBCL studies is underreported, particularly in global trials. If this information was reported and reflective of LBCL in clinical practice in the US, the numbers of Asian and Black patients would be low at ≤8%, and most patients would be expected to be White and non-Hispanic. [Table: see text]