Large clones of Clonal Hematopoiesis affect outcome in Mantle Cell Lymphoma: Results from The FIL MCL0208 Clinical Trial. in Blood advances / Blood Adv. 2025 Jan 14:bloodadvances.2024014948. doi: 10.1182/bloodadvances.2024014948.
2025
AOU Alessandria
AOU Città della Salute di Torino
AOU Alessandria
AOU Città della Salute di Torino
Tipo pubblicazione
Journal Article
Autori/Collaboratori (30)Vedi tutti...
da Silva MG
Instituto Portugues de Oncologia de Lisboa - Francisco Gentil, Lisbon, Portugal.
Zilioli VRR
ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Balzarotti M MD
IRCCS Humanitas Clinical and Research Center, Rozzano, Italy.
et alii...
Instituto Portugues de Oncologia de Lisboa - Francisco Gentil, Lisbon, Portugal.
Zilioli VRR
ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Balzarotti M MD
IRCCS Humanitas Clinical and Research Center, Rozzano, Italy.
et alii...
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 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.
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PMID : 39808795
DOI : 10.1182/bloodadvances.2024014948