# Optimally Delivered R-da-EPOCH Versus R-CHOP-21 in Primary Mediastinal Large B-Cell Lymphoma: A Real-Life Comparison in a Single Academic Center

## TL;DR

This study compares two chemotherapy regimens for treating a specific type of lymphoma and finds that one regimen, R-da-EPOCH, leads to better outcomes with less need for additional radiation therapy.

## Contribution

The study provides real-life evidence that R-da-EPOCH offers superior disease control and survival in primary mediastinal large B-cell lymphoma compared to R-CHOP-21.

## Key findings

- R-da-EPOCH achieved a 5-year freedom from progression of 91% compared to 69% with R-CHOP-21.
- R-da-EPOCH reduced the need for radiotherapy from 69% to 6% among responders.
- Multivariate analysis confirmed R-da-EPOCH's superiority in freedom from progression and favorable outcomes for event-free and overall survival.

## Abstract

R-CHOP + consolidative radiotherapy (RT) has been historically the usual treatment option for PMLBCL with a cure rate of 75–80%. The National Cancer Institute introduced the intensified R-da-EPOCH regimen, which produced better outcomes compared to R-CHOP, while minimizing RT. However, there is no direct randomized comparison of R-da-EPOCH vs. R-CHOP and the majority of the comparative supporting data comes from retrospective series, where the comparisons performed demonstrated only marginally better outcomes. Herein, we report a large, real-life, single-center study aiming to compare R-da-EPOCH with R-CHOP in patients with PMLBCL of a single referral center, where the R-da-EPOCH escalation schedule was strictly followed almost universally. According to our findings, R-da-EPOCH if delivered optimally, eliminates the need for RT and might provide a benefit in disease control and potentially improved survival at the expense of a small, but measurable risk of long-term side effects.

Background/Objectives: The National Cancer Institute introduced the intensified R-da-EPOCH regimen in primary mediastinal large B-cell lymphoma (PMLBCL) to improve outcomes while minimizing radiotherapy use. However, there is no randomized comparison of R-da-EPOCH vs. R-CHOP-21. The objective of this study was to compare R-da-EPOCH with R-CHOP-21 in consecutive patients with PMLBCL of a single, large referral center, where the R-da-EPOCH escalation schedule was strictly followed. Methods: We retrospectively analyzed all 35 consecutive patients who received R-da-EPOCH (2017–2022) compared to 35 consecutive patients treated with R-CHOP-21 arm at the same Department, starting from the most recent patient and going backwards (2005–2017). Results: R-da-EPOCH was given strictly in 33/35 (94%) patients. The 5-year freedom from progression (FFP) was 91% vs. 69% (p = 0.027). The 5-year event-free survival (EFS) was 84% vs. 69% (p = 0.124). The 5-year overall survival (OS) was 97% vs. 80% (p = 0.063). Among R-CHOP-21-responders, 20/29 (69%) received RT compared to 2/34 (6%) R-da-EPOCH-responders. In multivariate analysis, R-da-EPOCH remained better than R-CHOP-21 in terms of FFP [hazard ratios (HRs) 0.21–0.26, all p < 0.05] and was associated with very favorable HR for EFS and OS. Conclusions: Optimally delivered R-da-EPOCH minimized the use of RT in a real-life setting and provided superior outcomes than R-CHOP-21.