# Protocol digest of a randomized phase III study of pola-R-CHP/high-dose methotrexate/IT vs. pola-R-CHP/IT for newly diagnosed diffuse large B-cell lymphoma with high risk of central nervous system relapse: JCOG2201 (PREMIER)

## TL;DR

This clinical trial compares two treatment regimens for high-risk diffuse large B-cell lymphoma to prevent central nervous system relapse.

## Contribution

The study introduces a novel approach by evaluating high-dose methotrexate in early cycles for CNS prophylaxis in DLBCL.

## Key findings

- The trial will enroll 390 patients across 52 institutions over four years.
- The primary endpoint is progression-free survival to assess treatment efficacy.

## Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Central nervous system (CNS) relapse is an uncommon yet lethal event in patients with DLBCL. Polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone (pola-R-CHP) is a standard of care for patients with untreated DLBCL. In patients with DLBCL at high risk of CNS relapse, the intrathecal (IT) administration of methotrexate and cytarabine is widely adopted for CNS prophylaxis; however, the optimal treatment is unclear. The aim of this multicenter randomized phase III trial is to confirm the superiority of high-dose methotrexate administered during early cycles of pola-R-CHP in addition to IT chemotherapy for patients with untreated DLBCL at high risk of CNS relapse. A total of 390 patients from 52 institutions will be enrolled across a 4-year period. The primary endpoint is progression-free survival. This trial was registered in the Japan Registry of Clinical Trials as jRCTs031230505 [https://jrct.mhlw.go.jp/latest-detail/jRCTs031230505].

This randomized phase III trial aims to confirm the superiority of high-dose methotrexate administered in addition to pola-R-CHP plus IT chemotherapy for DLBCL with a high risk of CNS relapse.