Comparison of Clinical Outcomes in Patients with Relapsed/refractory Large B‐cell Lymphoma Treated with Epcoritamab Versus Chemoimmunotherapy

Introduction: There is currently no clear standard of care for patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who have failed ≥2 prior lines of therapy (LOTs); although chemoimmunotherapy (CIT) regimens are the most commonly used therapies, outcomes are not optimal. Epcoritamab has demonstrated deep and durable responses among patients with R/R LBCL. We compared 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 collected in the COTA electronic health records database. The CIT cohort included adult patients diagnosed with LBCL and treated with CIT between January 2010 and March 2022 after failing ≥2 prior LOTs. Inverse probability of treatment weighting (IPTW) was used to create balanced cohorts based on demographic and clinical characteristics and outcomes were compared across these 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 with all 157 patients treated with epcoritamab for LBCL. Both cohorts 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 versus the CIT cohort (63.1% vs. 41.8%). CR rate was also higher in the epcoritamab cohort versus the CIT cohort (38.9% vs. 9.4%). Adjusted odds ratio (95% CI) for ORR and CR rate in the epcoritamab versus 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 versus the CIT cohort (2.6 mo [1.65, 2.84]). Adjusted hazard ratio (HR) (95% CI) for PFS in the epcoritamab versus CIT cohorts was 0.48 (0.37, 0.63; P < 0.0001). With the median OS for epcoritamab not reached at the time versus 4.9 mo for CIT, the adjusted HR (95% CI) for OS in the epcoritamab versus CIT cohorts was 0.5 (0.37, 0.69; P < 0.0001). Conclusions: Compared with CIT, epcoritamab significantly increased the likelihood of achieving response and reduced the risk of progression and mortality. These results underscore the therapeutic benefits of epcoritamab in R/R LBCL in the third-line or later setting. Comparative analyses conducted outside of a randomized clinical trial are subject to limitations. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Genmab A/S and AbbVie Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies, Immunotherapy Conflicts of interests pertinent to the abstract. A. Ip Consultant or advisory role: Secura Bio, AstraZeneca, TG Therapeutics Honoraria: Pfizer Other remuneration: Speakers Bureau: Seagen A. Rosenthal Other remuneration: Educational Sessions: Curio Science, MJH Health Sciences A. Mutebi Employment or leadership position: Genmab T. Wang Employment or leadership position: Genmab M. Jun Employment or leadership position: Genmab A. Wang Employment or leadership position: AbbVie J. Yu Employment or leadership position: AbbVie S. Brodkin Employment or leadership position: Genmab M. Sacchi Employment or leadership position: Genmab A. Kalsekar Employment or leadership position: Genmab J. Munoz Consultant or advisory role: Pharmacyclics/AbbVie, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, BMS, Kyowa, Alexion, Fosun Kite, Innovent, Seattle Genetics, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, BeiGene, Servier, Novartis, MorphoSys/Incyte, Secura Bio, TG Therapeutics, MEI, Lilly/Loxo Honoraria: Targeted Oncology, OncView, Curio, Kyowa, Physicians’ Education Resource, Seattle Genetics Research funding: Bayer, Gilead/Kite Pharma, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium Other remuneration: Speaker’s Bureau: Gilead/Kite Pharma, Kyowa, Bayer, Pharmacyclics/Janssen, Seattle Genetics, Acrotech/Aurobindo, BeiGene, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche