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

<b>Background and Objectives</b>: 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)). <b>Materials and Methods</b>: RNA was extracted from 65 relapse samples consisting of first-relapse LN samples (<i>n</i> = 20) from patients who previously underwent first-line treatment in the MCL2 and MCL3 trials, and either BM (<i>n</i> = 34) or PB (<i>n</i> = 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. <b>Results</b>: 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, <i>p</i>-value 0.0407) and overall survival (OS) (HR 2.29, <i>p</i>-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 <i>TP53</i> mutation status. <b>Conclusions</b>: 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.