MIPI53. A NEW PROGNOSTIC INDEX FOR MANTLE CELL LYMPHOMA

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Introduction: Mantle Cell Lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma with an overall survival (OS) of more than 5 years with optimal treatment, but with a highly heterogeneous clinical behavior. The Mantle Cell Lymphoma International Prognostic Index (MIPI) allows risk stratification of patients based on clinical variables and is widely used to establish the prognosis of these patients. However, there are still certain limitations, such as the presence of low-risk MIPI patients who exhibit aggressive behavior. The inclusion of molecular markers could improve stratification models. Our objective was to analyze the role of TP53 mutations in MCL patients and combine it with clinical variables to establish a prognostic model that improves MIPI. We evaluated response to first-line treatment, progression-free survival (PFS), and overall survival (OS). Patients and Methods: We included 115 patients diagnosed of MCL between 2003 and 2022 with t(11;14) demonstrated by FISH and/or PCR. TP53 variants (single nucleotide polymorphism and insertions/deletions) were studied using the International Agency for Research on Cancer (IARC) Sanger sequencing protocols, evaluating the prognostic value of each alteration using the Seshat database. Survival analyses were performed using Kaplan-Meier curves and the log-rank test. Untreated patients were excluded from PFS. A multivariate model was generated using the Cox regression method. MIPI 53 model was developed using Cox Regression coefficients to correlate significant variables. Patient groups were distributed following the minimal p-value approach. MIPI53 and MIPI was compared using Akaike information criterion (AIC). Results: Median age of the patients was 64 years, with a 3:1 male-female distribution. The median follow-up of the series was 67.8 months. Patients with TP53 mutations had lower overall response rate to first line (65% vs. 89%, p < 0.05), lower 5-year PFS (30% vs. 66%, p < 0.0001), and lower 5-year OS (52% vs. 91%, p < 0.0001). N = 80 patients were included in the multivariate analysis. TP53 mutations (HR: 8.3, 95% CI: 3.1-21.8), ECOG>1 (HR: 4.4, 95% CI: 1.2-16.7), LDH levels (HR: 9.0, 95% CI: 1.1-78.7), and age (HR: 1.1, 95% CI: 1.0-1.1) were associated with lower OS (p < 0.05 for all variables). These results allowed the construction of a new prognostic model, MIPI53, which was able to separate the patients into 3 groups with different PFS (78% vs. 48% vs. 13% at 5 years, p < 0.001) and OS (100% vs. 85% vs. 27% at 5 years; p < 0.0001). The MIPI53 model showed a better fit than the MIPI regarding PFS (AIC 240.9 vs. 245.9) and OS (AIC 120.25 vs 135.85). Conclusions: The combination of TP53 mutations with clinical variables seems to improve the prognostic value of MIPI. A further external validation is required to assess its potential application in clinical routine. Keywords: aggressive B-cell non-Hodgkin lymphoma, risk models, diagnostic and prognostic biomarkers No conflicts of interests pertinent to the abstract.

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