Background: Peripheral T-cell lymphomas (PTCLs) comprise < 10% of non-Hodgkin lymphomas with pronounced genomic heterogeneity. The prognostic impact of KMT2A rearrangements in real-world Asian cohorts remains underexplored.
Objectives: To define progression-free survival (PFS) and overall survival (OS) in PTCL patients and determine prognostic impact of mutations detected by targeted next-generation sequencing (NGS).
Methods: We retrospectively analyzed 55 consecutive adults with histologically confirmed PTCL (PTCL-NOS: 23, AITL: 14, ENKTL: 11) diagnosed between September 2020-2024. Specimens were analyzed using 146-gene hybrid-capture NGS panel. Clinical data including demographics, therapy, and responses were collected.
Results: With median follow-up of 21 months (range: 6-49), 2-year OS was 57.3% (95% CI: 43.9-74.6%). Most common mutations were ATR (43.2%), KMT2A (24.3%), and TP53 (13.5%). KMT2A mutations in 15 patients (27%) were associated with significantly worse OS (median: 10.7 vs. 30.8 months, p=0.043) and PFS (median: 5.9 vs. 12.5 months, p=0.039). DNMT3A mutations also showed inferior OS compared to wild-type (p=0.027), while TET2 mutations (p=0.9) showed no significant survival differences. Ten patients (18%) received brentuximab-based therapy; however, this did not confer survival benefit compared to standard chemotherapy. Multivariable analysis confirmed KMT2A mutations as independent predictor of inferior PFS (HR: 2.56, 95% CI: 1.02-6.45), suggesting KMT2A-mutated PTCL represents a high-risk molecular subgroup requiring novel therapeutic strategies.
Conclusions: KMT2A mutations occur in one-quarter of PTCL patients and confer significantly worse prognosis. These findings underscore importance of NGS-based genomic profiling for risk stratification in PTCL. Prospective studies are needed to validate results and explore targeted therapeutic approaches for KMT2A-mutated patients.
