Epcoritamab Plus Gemcitabine and Oxaliplatin Versus Glofitamab or Rituximab Plus Gemcitabine and Oxaliplatin in Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: A Match-Adjusted Comparative Analysis

Introduction: Epcoritamab (Epcor) is a novel subcutaneous CD3xCD20 bispecific antibody (bsAb) that is currently approved as monotherapy for the treatment of adults with relapsed or refractory (R/R) large B-cell lymphoma after ≥2 systemic therapies. The combination of Epcor with standard treatment regimens has been shown to be safe and efficacious; Epcor in combination with gemcitabine and oxaliplatin (Epcor+GemOx) has provided deep and durable responses with favorable survival outcomes in a transplant-ineligible R/R diffuse large B-cell lymphoma (DLBCL) patient (pt) population, of which 99% were from the US and Europe (EPCORE NHL-2; NCT04663347). Another CD3xCD20 bsAb, intravenous glofitamab, has been studied in combination with gemcitabine and oxaliplatin (Glofi+GemOx) in the randomized STARGLO trial (NCT04408638) and demonstrated benefit over rituximab plus GemOx (R-GemOx), despite not demonstrating superiority over R-GemOx in patients from the US and Europe. In the absence of head-to-head data, this study used matching-adjusted indirect comparisons (MAICs) to assess the comparative efficacy of Epcor+GemOx vs R-GemOx and vs Glofi+GemOx.

Methods: Individual pt-level data from EPCORE NHL-2 arm 5 and aggregated data from pts in each of the STARGLO arms were used to conduct an MAIC. Logistic propensity score models were used to weight Epcor+GemOx-treated pts to create matched cohorts with the R-GemOx and Glofi+GemOx arms separately. Weighting was conducted based on the distribution of baseline characteristics and prognostic factors such as age, sex, Eastern Cooperative Oncology Group performance status, previous therapies, and primary refractory status. Overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), and overall survival (OS) were compared for Epcor+GemOx vs R-GemOx, and vs Glofi+GemOx.

Results: A total of 103 pts treated with Epcor+GemOx (median follow-up: 13.2 months) were compared to 91 pts treated with R-GemOx and 183 pts treated with Glofi+GemOx (median follow-up: 20.7 months), although differences in median follow-up time limited comparisons of longer-term survival outcomes. Match-adjustment mitigated differences in baseline characteristics across the 3 cohorts.

After adjustment, Epcor+GemOx demonstrated a significant 44.8% advantage in ORR over R-GemOx (85.4% vs 40.7%), with a 110% increase in the likelihood of achieving a response (odds ratio [OR] 2.1; 95% CI 1.6-2.8; P<0.0001). Epcor+GemOx also demonstrated a significant 43.2% advantage in CR rate over R-GemOx (68.5% vs 25.3%), with a 170% increase in the likelihood of achieving a CR (OR 2.7; 95% CI 1.8-4.1; P<0.0001). With the current follow-up, Epcor+GemOx demonstrated superior PFS vs R-GemOx (hazard ratio [HR] 0.37; 95% CI 0.22-0.63; P<0.001), corresponding to a 63% reduction in the risk of progression. Median OS was not reached [NR] for Epcor+GemOx vs 13.9 months for R-GemOx, corresponding to a 43% reduction in the risk of mortality (HR 0.57 [95% CI 0.33-0.98]; P=0.04).

After adjustment, Epcor+GemOx demonstrated a significant 15% advantage in ORR over Glofi+GemOx (83.3% vs 68.3%), with a 20% increase in the likelihood of achieving a response (OR 1.2; 95% CI 1.0-1.4; P=0.021). Epcor+GemOx demonstrated a trend toward higher CR rate than Glofi+GemOx (66.8% vs 58.5%; OR 1.1; 95% CI 0.90-1.5; P=0.277). Adjusted median PFS and OS for Epcor+GemOx, with limited follow-up and substantial censoring, was 12.9 months and NR, respectively. For Glofi+GemOx with longer follow-up, PFS and OS were 13.8 months and 25.6 months, respectively.

Conclusions: Results show significantly superior efficacy for all outcomes with Epcor+GemOx vs R-GemOx from STARGLO. Epcor+GemOx also provided superior ORR and a trend toward higher CR rates vs Glofi+GemOx, indicating potential for better long-term efficacy outcomes. The Epcor+GemOx survival data are still maturing given shorter follow-up time, preventing a robust comparison of survival vs Glofi+GemOx. Findings support the efficacy of Epcor+GemOx as an alternative therapeutic regimen in transplant-ineligible patients with R/R DLBCL.

Ip:AstraZeneca: Consultancy, Honoraria; Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; COTA: Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Speakers Bureau; MJH life sciences Graticule: Consultancy, Honoraria; Seagen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Munoz:Targeted Oncology: Honoraria; Physicians' Education Resource: Honoraria; OncView: Honoraria; Curio: Honoraria; Portola: Research Funding; Merck: Research Funding; Bayer: Consultancy, Research Funding; Eli Lilly: Consultancy; AstraZeneca: Consultancy; TG Therapeutics: Consultancy; MEI: Consultancy; Morphosys/Incyte: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Epizyme: Consultancy; ADC Therapeutics: Consultancy; Genentech/Roche: Consultancy, Research Funding; Genzyme: Consultancy; Genmab: Consultancy; Verastem: Consultancy, Research Funding; Aurobindo: Consultancy; Karyopharm: Consultancy; Seattle Genetics: Consultancy, Research Funding; Fosunkite: Consultancy; Alexion: Consultancy; Kyowa: Consultancy; Celgene/Bristol Myers Squibb: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Pfizer: Consultancy; Janssen: Consultancy, Research Funding; Gilead/Kite: Consultancy, Research Funding; Pharmacyclics/Abbvie, Bayer, Gilead/Kite, Beigene, Pfizer, Janssen, Celgene/Bristol Myers Squibb, Kyowa, Alexion, Fosunkite, Seattle Genetics, Karyopharm, Aurobindo, Verastem, Genmab, Genzyme, Genentech/Roche, ADC Therapeutics, Epizyme, Beigene, Novartis,: Consultancy; Alexion: Consultancy; BeiGene: Consultancy; Pharmacyclics/Abbvie: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Targeted Oncology, OncView, Curio, Genzyme, and Physicians' Education Resource.: Honoraria; Bayer, Gilead/Kite, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium, Novartis, Beigene.: Research Funding. Rosenthal:RMEI, Curio Science, Targeted Oncology, OncLiveU: Other: Educational Workshop Speaker Role. Darrah:Kite, MorphoSys: Membership on an entity's Board of Directors or advisory committees. Wang:Genmab: Current Employment, Current equity holder in publicly-traded company. Zhang:Genmab: Current Employment, Current equity holder in publicly-traded company. Mutebi:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Jun:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Ding:Genmab: Current Employment, Current equity holder in publicly-traded company. Chhibber:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Rivas Navarro:Genmab: Current Employment, Current equity holder in publicly-traded company. Risum:Genmab: Current Employment, Current equity holder in publicly-traded company. Atiya:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: stockholder of Genmab. Brodkin:Genmab: Current Employment, Current equity holder in publicly-traded company. Wang:AbbVie: Current Employment, Current equity holder in publicly-traded company, Other: stockholder of AbbVie. Alshreef:AbbVie: Current Employment, Current equity holder in publicly-traded company, Other: stockholder. Harb:AbbVie: Current Employment, Current equity holder in publicly-traded company, Other: stockholder of AbbVie. Sacchi:Genmab: Current Employment, Current equity holder in publicly-traded company, Other: owns Genmab stock. Hoehn:Genmab: Current Employment, Current equity holder in publicly-traded company. Karimi:Roche/Genentech: Other: Travel Expenses, Research Funding; Xencor: Research Funding; Lilly/Loxo: Research Funding; Merck: Research Funding; ADC Therapeutics: Consultancy, Honoraria; AstraZeneca: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding.