# Exploring the Prognostic Potential of circSCORE in Patients with Relapsed/Refractory Mantle Cell Lymphoma

## TL;DR

This study shows that a circular RNA-based score, circSCORE, can predict outcomes in patients with relapsed or refractory mantle cell lymphoma, including in non-nodal tissues.

## Contribution

The study is the first to validate circSCORE as a prognostic biomarker in relapsed/refractory mantle cell lymphoma using non-nodal tissues.

## Key findings

- High circSCORE was associated with worse progression-free and overall survival in relapsed/refractory MCL patients.
- circSCORE retained prognostic value for progression-free survival even after adjusting for other clinical factors.
- The score showed similar trends in non-nodal tissues like bone marrow and peripheral blood.

## Abstract

Background and Objectives: Mantle cell lymphoma (MCL) is a highly heterogenous disease, but an optimal prognostic biomarker in relapsed/refractory (R/R) MCL has not yet been established. The circular RNA-based risk score, circSCORE, was recently proposed as a promising prognosticator in newly diagnosed, younger patients with MCL. This study explores the prognostic potential of circSCORE in R/R MCL in both nodal (lymph node (LN)) and non-nodal tissues (bone marrow (BM)) and peripheral blood (PB)). Materials and Methods: RNA was extracted from 65 relapse samples consisting of first-relapse LN samples (n = 20) from patients who previously underwent first-line treatment in the MCL2 and MCL3 trials, and either BM (n = 34) or PB (n = 11) samples obtained from patients with R/R MCL included in the MCL6 trial, taken at trial baseline. Kaplan–Meier estimates, and Cox regressions were used to evaluate the association between circSCORE risk groups (high versus low) and outcomes. Results: Survival analyses showed significantly inferior outcomes for patients with high-risk circSCORE compared to low-risk score for both progression-free survival (PFS) (hazard ratio (HR) 1.99, p-value 0.0407) and overall survival (OS) (HR 2.29, p-value 0.0192) in the total cohort. The same tendencies were displayed when exploring the non-nodal samples only. Furthermore, circSCORE retained prognostic impact for PFS, but not OS, when adjusted for Ki67, MIPI, and TP53 mutation status. Conclusions: The circRNA-based risk score, circSCORE, displayed prognostic potential in R/R MCL along with promising application in non-nodal tissues, indicating that circSCORE, if further validated, might serve as an easily obtainable biomarker in R/R MCL.