Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial

Large clones of clonal hematopoiesis affect outcome in mantle cell lymphoma: results from the FIL MCL0208 clinical trial

Abstract: Although recent evidence suggests that myeloid clonal hematopoiesis (M-CH) may influence lymphoma clinical outcome, its impact in mantle cell lymphoma (MCL) remains unclear. Here, we report a comprehensive next-generation sequencing–based analysis of the M-CH mutational landscape at baseli...

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Main Authors: Simone Ragaini, Anna Galli, Elisa Genuardi, Martina Gandossini, Beatrice Alessandria, Aurora Maria Civita, Andrea Evangelista, Enrico Amaducci, Vittorio Stefoni, Federica Cavallo, Filippo Ballerini, Benedetta Puccini, Daniele Vallisa, Mariagrazia Michieli, Anna Pascarella, Angelo Palmas, Caterina Patti, Elisa Lucchini, Maria Grazia Careddu, Michele Merli, Massimiliano Postorino, Carola Boccomini, Monica Balzarotti, Vittorio Ruggero Zilioli, Maria Gomes da Silva, Benedetto Bruno, Ettore Rizzo, Marco Ladetto, Luca Malcovati, Simone Ferrero
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952925000175
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Summary:Abstract: Although recent evidence suggests that myeloid clonal hematopoiesis (M-CH) may influence lymphoma clinical outcome, its impact in mantle cell lymphoma (MCL) remains unclear. Here, we report a comprehensive next-generation sequencing–based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi MCL0208 phase 3 trial, evaluating lenalidomide maintenance vs observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young patients with MCL. Overall, 254 of 300 (85%) enrolled patients (median age, 57 years [range, 32-66]) had a baseline sample available for CH analysis. Using stringent criteria, at least 1 mutation involving M-CH candidate genes was described in 34 patients (13%), with DNMT3A being the most frequently mutated gene (54%). After a median follow-up of 7 years, the presence of large CH clones (variant allele frequency of ≥10%) predicted worse progression-free survival (hazard ratio [HR], 2.93; 95% confidence interval [CI] 1.36-6.31; P = .006) and overall survival (HR, 3.02 [1.21-7.55]; P = .018) compared with patients with CH. Importantly, the competing risks analysis demonstrates that the worse clinical outcome associated with M-CH large clones is linked to MCL progression (P < .05). Moreover, large M-CH clones showed longer time to hematological recovery after ASCT than the remaining cohort (P = .026). In conclusion, we showed for the first time that large CH clones might associate with unfavorable clinical impact in patients with MCL. This trial was registered at www.clinicaltrialsregister.eu as EudraCT (2009-012807-25) and www.ClinicalTrials.gov as #NCT02354313.
ISSN:2473-9529

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