Dissecting minimal residual disease dynamics to improve outcome prediction in mantle cell lymphoma: Data from the Fondazione Italiana Linfomi (FIL)‐MCL0208 clinical trial

Recent clinical trials have underscored the value of repeated minimal residual disease (MRD) measurements as a highly sensitive method for detecting subclinical disease and enabling dynamic risk stratification in hematologic malignancies. Despite its clinical potential, the complex and heterogeneous nature of MRD kinetics presents significant challenges for interpreting and integrating it into routine clinical decision-making. In this study, we present a comprehensive, model-based workflow for the longitudinal analysis of MRD trajectories designed to improve relapse risk prediction. We applied this newly developed workflow to a cohort of patients with mantle cell lymphoma (MCL). MRD measurements were collected from both bone marrow (BM) and peripheral blood (PB) over time, stored in the Fondazione Italiana Linfomi MCL0208 clinical trial. Using our functional MRD workflow, we defined four MRD dynamics that collapsed into two clinically relevant groups: favorable (rapid, sustained negativization) and unfavorable (persistent or fluctuating MRD). Patients with unfavorable profiles showed significantly shorter time to progression (TTP), with hazard ratio (HR) = 4.18 (95% CI: 2.44-7.14) in BM and HR = 5.71 (95% CI: 2.86-11.42) in PB. External validation in the European MCL Network "Younger trial" confirmed the predictive power of this stratification, with Kaplan-Meier analyses demonstrating significant prognostic discrimination. The most informative temporal windows for patient clustering vary by tissue. Early-phase BM assessments offer greater discriminatory power, whereas late-phase assessments are most informative in PB. These findings indicate that longitudinal MRD assessment in PB represents a clinically actionable strategy that could reduce dependence on invasive BM procedures.

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Journal
HemaSphere
Published
2026-04-30
DOI
https://doi.org/10.1002/hem3.70375
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
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article

Dissecting minimal residual disease dynamics to improve outcome prediction in mantle cell lymphoma: Data from the Fondazione Italiana Linfomi (FIL)‐MCL0208 clinical trial

Marco Beccuti, Luca Arcaini, Monica Balzarotti, María Gomes da Silva et al.
HemaSphere
Lymphoma Diagnosis and Treatment
article

Dissecting minimal residual disease dynamics to improve outcome prediction in mantle cell lymphoma: Data from the Fondazione Italiana Linfomi (FIL)‐MCL0208 clinical trial

Marco Beccuti, Luca Arcaini, Monica Balzarotti, María Gomes da Silva, Vittorio Ruggero Zilioli, Eva Hoster, Andrea Evangelista, Vittorio Stefoni, Elisa Genuardi, Gian Maria Zaccaria, Alice Di Rocco, Francesca Cordero, Roberta Sirovich, Simone Ragaini, Elizabeth Macintyre, Dora Tortarolo, Simone Pernice, Aurora Maria Civita, Daniela Volpatto, Olivier Hermine, Melania Celli, Alessandro Re, Federica Cavallo, Marco Ladetto, Carola Boccomini, Simone Ferrero, Christiane Pott, Martin Dreyling
article en

Abstract

Recent clinical trials have underscored the value of repeated minimal residual disease (MRD) measurements as a highly sensitive method for detecting subclinical disease and enabling dynamic risk stratification in hematologic malignancies. Despite its clinical potential, the complex and heterogeneous nature of MRD kinetics presents significant challenges for interpreting and integrating it into routine clinical decision-making. In this study, we present a comprehensive, model-based workflow for the longitudinal analysis of MRD trajectories designed to improve relapse risk prediction. We applied this newly developed workflow to a cohort of patients with mantle cell lymphoma (MCL). MRD measurements were collected from both bone marrow (BM) and peripheral blood (PB) over time, stored in the Fondazione Italiana Linfomi MCL0208 clinical trial. Using our functional MRD workflow, we defined four MRD dynamics that collapsed into two clinically relevant groups: favorable (rapid, sustained negativization) and unfavorable (persistent or fluctuating MRD). Patients with unfavorable profiles showed significantly shorter time to progression (TTP), with hazard ratio (HR) = 4.18 (95% CI: 2.44-7.14) in BM and HR = 5.71 (95% CI: 2.86-11.42) in PB. External validation in the European MCL Network "Younger trial" confirmed the predictive power of this stratification, with Kaplan-Meier analyses demonstrating significant prognostic discrimination. The most informative temporal windows for patient clustering vary by tissue. Early-phase BM assessments offer greater discriminatory power, whereas late-phase assessments are most informative in PB. These findings indicate that longitudinal MRD assessment in PB represents a clinically actionable strategy that could reduce dependence on invasive BM procedures.

HemaSphereVol. 10(5)
Hôpital Necker-Enfants Malades (FR), Inserm (FR), Zimmer Biomet (Netherlands) (NL), Université Paris Cité (FR), University of Pavia (IT), LMU Klinikum (DE), Institut Necker Enfants Malades (FR), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), 5T Torino (Italy) (IT), Assistance Publique – Hôpitaux de Paris (FR), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), University Hospital Schleswig-Holstein (DE), Ospedale Infermi di Rimini (IT), Istituto Oncologico Romagnolo (IT), Policlinico San Matteo Fondazione (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo (IT), IRCCS Humanitas Research Hospital (IT), University of Turin (IT), Polytechnic University of Bari (IT), Ludwig-Maximilians-Universität München (DE), Sapienza University of Rome (IT), University of Lübeck (DE), University of Bologna (IT)
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