MATCH-ADJUSTED COMPARISON OF EPCORITAMAB VERSUS NON-ANTHRACYCLINE CHEMOIMMUNOTHERAPY IN NEWLY DIAGNOSED DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS WITH HIGH CARDIOVASCULAR RISK

IF 3.9 4区医学 Q2 HEMATOLOGY

Hematological Oncology Pub Date : 2025-06-16 DOI:10.1002/hon.70094_291

P. C. Johnson, E. Guo, G. Zhang, T. Wang, V. Patel, A. Mutebi, M. Atiya, J. Ukropec, A. Wang, S. Diness Vindeløv, J. Darrah

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Eur J Heart Fail 2020;22:1945) and based on age and/or presence of comorbidities, including heart failure, valvular disease, myocardial infarction, coronary revascularization, hypertension, diabetes, or kidney disease. Inverse probability of treatment weighting was used to balance treatment cohorts on key available variables: age, gender, Ann Arbor stage, HRCV score, and postdiagnosis time-to-treatment. The primary endpoint was overall survival (OS). Hazard ratios (HRs) were estimated by weighted Cox regression models; time-to-event Kaplan-Meier curves were compared using log-rank tests.Results: Eighty-one pts receiving non-AC CIT and 45 receiving epcor were included. Before adjustment, the epcor cohort had fewer females (60.0% vs. 70.4%), fewer pts aged ≥ 80 years (82.2% vs. 95.1%), fewer pts with Ann Arbor stage III/IV (66.7% vs. 72.8%), and lower mean HRCV score (7.0 vs. 8.4). Adjusted OS was significantly improved in epcor (median OS not evaluable) versus non-AC CIT cohorts (median OS 10.2; HR 0.30 [95% CI: 0.14–0.66; p = 0.0027]). Subgroup analyses were consistent for non-AC CIT regimens: epcor versus R-CVP/R-CEOP (HR 0.34 [95% CI: 0.16–0.74]; p = 0.0067]) and epcor versus BR (HR 0.21 [95% CI: 0.08–0.56]; p = 0.0019) (Figures A–C).Conclusions: In the 1L treatment of DLBCL with HRCV status, epcor mono demonstrated significantly improved OS versus non-AC CIT. These findings highlight a critical unmet need for novel chemotherapy-free treatment options in this population.Research funding declaration: This study was funded by Genmab A/S and AbbVie.Keywords: Non-HodgkinPotential sources of conflict of interest:P. C. JohnsonConsultant or advisory role: AbbVie, ADC Therapeutics, AstraZeneca, Bristol Myers Squibb, Incyte, and SeagenOther remuneration: Research funding: AstraZeneca, Medically Home, Novartis, and OncternalE. GuoEmployment or leadership position: GenmabStock ownership: GenmabG. ZhangEmployment or leadership position: GenmabStock ownership: GenmabT. WangEmployment or leadership position: GenmabStock ownership: GenmabV. PatelEmployment or leadership position: GenmabStock ownership: GenmabA. MutebiEmployment or leadership position: GenmabStock ownership: GenmabM. AtiyaEmployment or leadership position: GenmabStock ownership: GenmabJ. UkropecEmployment or leadership position: GenmabStock ownership: GenmabA. WangEmployment or leadership position: AbbVieStock ownership: AbbVieS. Diness VindeløvEmployment or leadership position: GenmabStock ownership: GenmabJ. 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引用次数: 0

Abstract

Introduction: Anthracycline-containing (AC) chemoimmunotherapy (CIT) regimens may be unsuitable for patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who are older and/or have specific comorbidities, due to elevated risk of cardiovascular toxicities. Consequently, pts with high-risk cardiovascular (HRCV) status are often treated with non-AC CIT. In the EPCORE DLBCL-3 (NCT05660967) trial, epcoritamab (epcor) monotherapy (mono) showed promising efficacy and manageable safety in pts with newly diagnosed DLBCL and HRCV status (Morschhauser F et al. Blood. 2024;144:867). This analysis compares the efficacy of epcor mono versus non-AC CIT in pts with newly diagnosed DLBCL and HRCV status.

Methods: Individual pt data for first-line (1L) epcor from the EPCORE DLBCL-3 trial were compared with pts treated with 1L non-AC CIT in the real-world setting. Pts diagnosed with DLBCL from 2007–2017 were identified from the US National Cancer Institute Surveillance, Epidemiology, and End Results database for initial diagnosis records and linked to the US Medicare database for treatment details using diagnosis codes (ICD-O-3: 9680/9688). Non-AC CITs included R-CVP (rituximab, cyclophosphamide, vincristine sulfate, and prednisone) or R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, and oral prednisolone) and BR (bendamustine and rituximab). HRCV status was defined using the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology criteria (Lyon AR et al. Eur J Heart Fail 2020;22:1945) and based on age and/or presence of comorbidities, including heart failure, valvular disease, myocardial infarction, coronary revascularization, hypertension, diabetes, or kidney disease. Inverse probability of treatment weighting was used to balance treatment cohorts on key available variables: age, gender, Ann Arbor stage, HRCV score, and postdiagnosis time-to-treatment. The primary endpoint was overall survival (OS). Hazard ratios (HRs) were estimated by weighted Cox regression models; time-to-event Kaplan-Meier curves were compared using log-rank tests.

Results: Eighty-one pts receiving non-AC CIT and 45 receiving epcor were included. Before adjustment, the epcor cohort had fewer females (60.0% vs. 70.4%), fewer pts aged ≥ 80 years (82.2% vs. 95.1%), fewer pts with Ann Arbor stage III/IV (66.7% vs. 72.8%), and lower mean HRCV score (7.0 vs. 8.4). Adjusted OS was significantly improved in epcor (median OS not evaluable) versus non-AC CIT cohorts (median OS 10.2; HR 0.30 [95% CI: 0.14–0.66; p = 0.0027]). Subgroup analyses were consistent for non-AC CIT regimens: epcor versus R-CVP/R-CEOP (HR 0.34 [95% CI: 0.16–0.74]; p = 0.0067]) and epcor versus BR (HR 0.21 [95% CI: 0.08–0.56]; p = 0.0019) (Figures A–C).

Conclusions: In the 1L treatment of DLBCL with HRCV status, epcor mono demonstrated significantly improved OS versus non-AC CIT. These findings highlight a critical unmet need for novel chemotherapy-free treatment options in this population.

Research funding declaration: This study was funded by Genmab A/S and AbbVie.

Keywords: Non-Hodgkin

Potential sources of conflict of interest:

P. C. Johnson

Consultant or advisory role: AbbVie, ADC Therapeutics, AstraZeneca, Bristol Myers Squibb, Incyte, and Seagen

Other remuneration: Research funding: AstraZeneca, Medically Home, Novartis, and Oncternal

E. Guo