Development and validation of a novel prognostic index for mantle cell lymphoma integrating TP53 mutations (MIPI53)

: Mantle cell lymphoma (MCL) is a clinically heterogeneous disease with varying treatment responses and outcomes. Despite the utility of the Mantle Cell Lymphoma International Prognostic Index (MIPI), its predictive capacity can be enhanced by integrating genetic markers such as TP53 mutations. We analysed 143 newly diagnosed MCL patients from a real-world cohort, assessing TP53 mutational status, clinical and biological markers. We developed the MIPI53 index by incorporating TP53 mutations, lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) status and age. Internal validation was performed via bootstrapping, and external validation was conducted with data from the fondazione Italiana Linfomi (FIL) MCL0208 trial. Patients were stratified into low-, intermediate- and high-risk groups, showing significant differences in 5-year progression-free survival (PFS) (83.1%, 35.4% and 12.0%, respectively; p < 0.0001) and 5-year overall survival (OS) (92.1%, 80.5% and 33.8%, respectively; p < 0.0001). External validation confirmed the robustness of the model (c-index: 0.732; akaike information criterion, AIC: 296.2 according to OS). A simplified version (sMIPI53) was developed, maintaining high predictive accuracy in both training (c-index: 0.819; AIC: 404.5) and external cohort (c-index: 0.730; AIC: 296.7). The MIPI53 index effectively stratifies MCL patients into prognostic groups by integrating genetic and clinical variables to enhance outcome prediction.