Molecular biomarkers as key determinants of outcome in mantle cell lymphoma: results from the FIL V-RBAC trial.

Authors

Riccardo Moia, Mohammad Almasri, Maria Elena Carazzolo, Luca Cividini, Valentina Tabanelli, Federica Melle, Elisa Genuardi, Chiara Cosentino, Nawar Maher, Matteo Bellia, Abdurraouf Mokhtar Mahmoud, Andrea Evangelista, Francesca Maria Quaglia, Stefano Fiori, Riccardo Bomben, Maria Chiara Tisi, Marcello Riva, Anna Merli, Francesco Di Rotondo, Paolo Corradini, Lucia Farina, Claudia Castellino, Alessia Castellino, Vittorio Ruggero Zilioli, Cristina Muzi, Francesco Piazza, Alessandro Re, Stefan Hohaus, Francesca Gaia Rossi Dardanoni, Gerardo Musuraca, Alice Di Rocco, Benedetta Puccini, Roberta Sciarra, Filippo Ballerini, Federica Cavallo, Riccardo Bruna, Alessia Moioli, Andrea Bernardelli, Caterina Patti, Jacopo Olivieri, Benedetta Bianchi, Giacomo Loseto, Michele Spina, Sara Veronica Usai, Piero Maria Stefani, Caterina Stelitano, Daniela Drandi, Pier Luigi Zinzani, Andrés J M Ferreri, Monica Balzarotti, Marco Ladetto, Simone Ferrero, Stefano A Pileri, Gianluca Gaidano, Carlo Visco

Published in

Blood advances. Jul 24, 2026. Epub Jul 24, 2026.

Abstract

The present study comprehensively dissects the molecular landscape of elderly mantle cell lymphoma (MCL) patients enrolled in the phase II V-RBAC trial of the Fondazione Italiana Linfomi. Of the 140 patients enrolled in the trial, 132 had available gDNA extracted from lymph node biopsies or bone marrow aspirates and were included in the analysis. A CAPP-Seq assay targeting 146 genes relevant to MCL pathogenesis was employed to identify gene mutations and copy number variations. ATM was the most frequently mutated gene, detected in 55 patients (41.7%), followed by TP53 and KMT2D in 31 patients (23.5%). ATM deletion was observed in 32 patients (24%), while CDKN2A loss in 29 (22%). Beyond TP53 mutations, three other molecular lesions, including CDKN2A loss, CD36 mutations and single-hit ATM abnormalities (either mutation or deletion) were independently associated with progression-free survival after adjustment for high-risk trial-defining features, namely Ki-67 >30% and blastoid variant. Notably, patients harboring single-hit ATM alterations without any additional risk factors achieved durable long-term remission, while CD36 mutations were associated with adverse survival. Both findings represent previously unrecognized aberrations that in this cohort independently and inversely associated with survival. The four variables were integrated into a 4-factor molecular prognostic model internally validated using a bootstrapping approach, which identified four distinct patient subgroups with significantly different outcomes. These findings support the importance of i) molecular profiling in MCL, ii) risk-adapted trials like V-RBAC, and iii) the integration of other biological markers with TP53 mutations for a more precise risk assessment in MCL. (NCT03567876).

PMID:
42498280
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.

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