Real-world experience with dose-adjusted EPOCH-R in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma: a multicenter analysis from Turkey

Abstract

Dose-adjusted EPOCH-R (DA-EPOCH-R) has demonstrated efficacy in aggressive B-cell lymphomas, yet comprehensive real-world data from multiple centers remains limited. We conducted a multicenter analysis to evaluate the efficacy and safety of DA-EPOCH-R in patients with Diffuse Large B-Cell Lymphoma (DLBCL) and Primary Mediastinal B-Cell Lymphoma (PMBL), with particular emphasis on molecular subgroups and risk stratification. Methods: In this multicenter retrospective cohort study, we analyzed 140 patients with DLBCL or PMBL who received DA-EPOCH-R between January 2015 and December 2020. Treatment consisted of DA-EPOCH-R for 6-8 cycles with dose adjustments based on nadir counts. Molecular profiling included MYC, BCL-2, and BCL-6 expression by immunohistochemistry and FISH analysis for gene rearrangements. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan-Meier method, with prognostic factors evaluated using Cox proportional hazards regression. Results: At a median follow-up of 52 months (range: 12-72 months), the 5-year EFS and OS rates were 67% and 74%, respectively. Survival outcomes significantly correlated with IPI risk groups: low-risk patients (n=35) achieved 5-year EFS/OS rates of 82%/88%, compared to 71%/78% for low-intermediate (n=42), 58%/65% for high-intermediate (n=39), and 45%/52% for high-risk patients (n=24) (p<0.001). Among molecular subtypes, double-expressor lymphomas (n=39) showed 5-year EFS/OS rates of 54%/61%, while triple-expressor cases (n=21) achieved 48%/55%. Outcomes were notably inferior in double-hit (n=17) and triple-hit lymphomas (n=11), with 5-year EFS/OS rates of 42%/49% and 35%/42%, respectively. Complete response rates varied by molecular subtype: double-expressor (62%), triple-expressor (55%), double-hit (50%), and triple-hit (45%). Dose modifications were most frequently required in cycle 2 (35% of patients), with decreasing frequency in subsequent cycles (28%, 22%, 15%, and 10% in cycles 3-6, respectively). Conclusions: This multicenter analysis demonstrates that DA-EPOCH-R provides favorable outcomes in aggressive B-cell lymphomas, with survival rates varying significantly by IPI score and molecular subtype. The regimen maintained significant efficacy in all subgroups, although double- and triple-hit lymphomas showed inferior outcomes. The reduced frequency of dose changes in subsequent cycles suggests acceptable tolerability. These findings provide important real-world evidence supporting high response rates with DA-EPOCH-R therapy in high-grade B-cell lymphomas, specifically diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma, thus reducing the need for radiotherapy and avoiding radiotherapy-associated toxicity.