THE EFFICACY OF SUBCUTANEOUS EPCORITAMAB VS STANDARD OF CARE (SCHOLAR-5) IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA AFTER ≥2 SYSTEMIC THERAPIES: AN INDIRECT TREATMENT COMPARISON

Epcoritamab (epcor) is a novel, subcutaneous (SC) CD3xCD20 bispecific antibody that has shown single-agent efficacy and manageable safety in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL). The EPCORE NHL-1 trial (NCT03625037) demonstrated that epcor provided deep and durable responses with a high overall response rate (ORR=82%) and complete response rate (CR=63%) in a population including difficult-to-treat pts with R/R FL after ≥2 systemic therapies (Linton et al, ASH 2023). SCHOLAR-5 (Ghione et al, 2023) is a real-world cohort of R/R FL pts treated with standard of care (SoC) after ≥2 prior lines of therapy (LoTs) from 2014 to 2020; SoC largely consisted of chemoimmunotherapy (CIT), but also included autologous stem cell transplant (ASCT) and immunomodulatory drugs in later LoTs. SCHOLAR-5 reported pt characteristics, response rates, and survival outcomes stratified by individual LoT (3, 4, or ≥5 LoTs). No head-to-head data are available comparing the efficacy of epcor with SoC treatment with CIT. We conducted an unanchored, matching-adjusted indirect comparison of the efficacy of epcor with SoC. Methods: Baseline characteristics and outcomes for a pooled cohort of pts initiating ≥3 LoTs in SCHOLAR-5 were generated using a weighted average based on the reported sample size for each LoT. The indirect comparison was conducted by adjusting for imbalances in the key baseline characteristics between individual pt- level data on 128 pts from EPCORE NHL-1 (data cutoff April 21, 2023; median follow-up 17.4 months) and 206 pts pooled from SCHOLAR-5 to create balanced cohorts based on: age ≥65 years, sex, ECOG performance status, disease stages III/IV, FLIPI ≥3, bulky disease, prior ASCT, prior CAR T therapy, progression within 24 months after first LoT (POD24), refractory to last LoT, and proportion with ≥3 prior LoTs. Propensity score weights resulting from the adjustment were applied to estimate odds ratios (OR) for ORR and CR rates, while survival outcomes were additionally adjusted for the impact of the COVID-19 pandemic. Weighted Cox proportional-hazards models were used to estimate progression-free survival (PFS) and overall survival (OS) between the 2 treatments. Results: Compared with SCHOLAR-5, more pts in EPCORE NHL-1 (N = 128) had ECOG performance status of 0 (54.7% vs 36.6%), FLIPI ≥3 (60.9% vs 35.4%), POD24 (52.3% vs 26.8%), prior CAR T therapy (4.7% vs 0.0%), and ≥3 prior LoTs (63.3% vs 57.6%). After adjustment, compared with SoC, pts treated with epcor had higher response rates (ORR: 90.9% vs 56.8%; OR = 7.58; p < 0.001; CR: 73.7% vs 32.0%; OR = 5.95; p < 0.001). Furthermore, epcor-treated pts had improved PFS (hazard ratio [HR]=0.32 [95% CI: 0.19, 0.56]; p < 0.001) and OS (HR = 0.31 [95% CI: 0.16, 0.63]; p = 0.001) vs SoC. Findings from this cross-study analysis indicate that epcoritamab in R/R FL pts with ≥2 prior LoTs provides significantly higher response rates and improved survival compared with SoC, largely represented by treatment with CIT. Notwithstanding limitations of treatment comparisons outside of a head-to-head randomized clinical trial, the findings underscore the therapeutic benefits of SC epcoritamab over SoC/CIT. Daniela Hoehn,7 - Genmab US Inc., Plainsboro, NJ, USA