P1169: comparison of real-world clinical outcomes in patients with relapsed/refractory large b-cell lymphoma treated with epcoritamab vs chemoimmunotherapy

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) experience substantial burden of disease and suboptimal clinical outcomes. There is currently no clear standard of care for patients with R/R LBCL who have failed ≥2 prior lines of therapy (LOT); although chemoimmunotherapy (CIT) regimens are the most commonly used therapies in this patient population and treatment setting, the outcomes are not optimal. Epcoritamab, a subcutaneously administered CD3xCD20 T-cell–engaging, bispecific antibody, has demonstrated deep and durable responses with a manageable safety profile across R/R LBCL patient populations including those with poor prognostic features. Aims: To compare the efficacy of epcoritamab with that of CIT in R/R LBCL. Methods: This indirect treatment comparison utilized individual patient data (IPD) from the EPCORE™ NHL-1 trial (NCT03625037) based on the January 2022 data cut, and longitudinal IPD from multiple US clinical centers (community and academic) collected in the COTA electronic health records database. The CIT cohort included adult patients ≥18 years of age diagnosed with LBCL and treated with CIT between January 2010 and March 2022 after failing ≥2 prior LOT. Inverse probability of treatment weighting (IPTW) was used to create balanced cohorts based on a number of demographic and clinical characteristics. Outcomes were compared across the balanced cohorts. Overall response rate (ORR) and complete response (CR) rate were compared using weighted logistic models, and progression-free survival (PFS) and overall survival (OS) were compared using weighted Cox proportional-hazard models. Results: A total of 179 patients were included in the CIT cohort and compared to all 157 patients treated with epcoritamab for LBCL in the EPCORE NHL-1 expansion cohort. The cohorts (epcoritamab vs CIT) were balanced on: absence of prior CAR T exposure (61.1% vs 62.2%); International Prognostic Index score ≥3 (52.2% vs 49.2%); primary refractory (61.2% vs 61.8%); refractory to last LOT (82.8% vs 85.3%); refractory to most recent anti-CD20–containing regimen (85.4% vs 83.7%); time since last LOT (6.1 vs 5.3 mo); sex/male (59.9% vs 63.5%); and age at diagnosis (62.3 vs. 60.3 years). ORR in the epcoritamab cohort was higher vs the CIT cohort (63.1% vs 41.8%). CR rate was also higher in the epcoritamab cohort (38.9%) vs the CIT cohort (9.4%). Adjusted odds ratio (95% CI) for ORR and CR rate in the epcoritamab vs CIT cohorts was 1.51 (1.20, 1.89; P=0.0004) and 4.12 (2.39, 7.09; P<0.0001), respectively. Median PFS (95% CI) for the epcoritamab cohort (4.4 mo [3.02, 7.85]) was higher vs the CIT cohort (2.6 mo [1.65, 2.84]). Adjusted hazard ratio (HR) (95% CI) for PFS in the epcoritamab vs CIT cohorts was 0.48 (0.37, 0.63; P<0.0001). With the median OS for epcoritamab not reached at the time vs 4.9 mo for CIT, the adjusted HR (95% CI) for OS in the epcoritamab vs CIT cohorts was 0.5 (0.37, 0.69; P<0.0001). Summary/Conclusion: Epcoritamab provides a significantly increased likelihood of achieving response vs CIT, and significantly reduces the risk of progression and mortality vs CIT. These results underscore the therapeutic benefits of epcoritamab in R/R LBCL in the third-line or later setting. The findings are subject to limitations common to comparative analyses conducted outside of a randomized clinical trial. Keywords: Bispecific, Chemotherapy, Real world data, Immunotherapy