TY - JOUR
T1 - Large clones of Clonal Hematopoiesis affect outcome in Mantle Cell Lymphoma: Results from The FIL MCL0208 Clinical Trial
AU - Ragaini, Simone
AU - Galli, Anna
AU - Genuardi, Elisa
AU - Gandossini, Martina
AU - Alessandria, Beatrice
AU - Civita, Aurora Maria
AU - Evangelista, Andrea
AU - Amaducci, Enrico
AU - Stefoni, Vittorio
AU - Cavallo, Federica
AU - Ballerini, Filippo
AU - Puccini, Benedetta
AU - Vallisa, Daniele
AU - Michieli, Mariagrazia
AU - Pascarella, Anna
AU - Palmas, Angelo D
AU - Patti, Caterina
AU - Lucchini, Elisa
AU - Careddu, Maria Grazia
AU - Merli, Michele
AU - Postorino, Massimiliano
AU - Boccomini, Carola
AU - Balzarotti, Monica
AU - Zilioli, Vittorio Ruggero Ruggero
AU - da Silva, Maria Gomes
AU - Bruno, Benedetto
AU - Rizzo, Ettore
AU - LADETTO, Marco
AU - Malcovati, Luca
AU - Ferrero, Simone
PY - 2025
Y1 - 2025
N2 - : 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 NGS-based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT02354313), evaluating lenalidomide maintenance versus observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young MCL patients. Overall, 254/300 (85%) enrolled patients (median age 57 years [32-66]) had a baseline sample available for CH analysis. Using stringent criteria, at least one 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 (VAF ≥ 10%) predicted worse PFS (HR 2.93 [1.36-6.31], p=0.006) and OS (HR 3.02 [1.21-7.55], p=0.018) compared to CH- patients. Importantly, the competing risks analysis demonstrates that the worse clinical outcome associated with M-CH large clones is linked to MCL progression (P<0.05). Moreover, large M-CH clones showed longer time to hematologic recovery after ASCT compared to the remaining cohort (p=0.026). In conclusion, we showed for the first time that large CH clones might associate with unfavorable clinical impact in MCL patients.
AB - : 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 NGS-based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT02354313), evaluating lenalidomide maintenance versus observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young MCL patients. Overall, 254/300 (85%) enrolled patients (median age 57 years [32-66]) had a baseline sample available for CH analysis. Using stringent criteria, at least one 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 (VAF ≥ 10%) predicted worse PFS (HR 2.93 [1.36-6.31], p=0.006) and OS (HR 3.02 [1.21-7.55], p=0.018) compared to CH- patients. Importantly, the competing risks analysis demonstrates that the worse clinical outcome associated with M-CH large clones is linked to MCL progression (P<0.05). Moreover, large M-CH clones showed longer time to hematologic recovery after ASCT compared to the remaining cohort (p=0.026). In conclusion, we showed for the first time that large CH clones might associate with unfavorable clinical impact in MCL patients.
UR - https://iris.uniupo.it/handle/11579/201982
U2 - 10.1182/bloodadvances.2024014948
DO - 10.1182/bloodadvances.2024014948
M3 - Article
SN - 2473-9537
JO - Blood advances
JF - Blood advances
ER -