UNVEILING THE PROGNOSTIC CHALLENGES OF NODAL PERIPHERAL T-CELL LYMPHOMAS: A MULTICENTER REAL-WORLD STUDY

Abstract

Introduction: Peripheral T-cell lymphomas (PTCL) are a rare group of malignancies derived from mature T-cells or natural killer cells, characterized by significant clinical-biological heterogeneity despite being grouped together. These entities have unique clinical, morphological, phenotypic, and molecular signatures. The predominantly nodal presentation group includes the histological variants ALK-positive anaplastic large cell lymphoma (ALK1+ ALCL), ALK-negative anaplastic large cell lymphoma (ALK1- ALCL), angioimmunoblastic T-cell lymphoma (AITL), and PTCL, not otherwise specified (PTCL-NOS). The central pillar of treatment for this subgroup of lymphomas is based on anthracycline-containing polychemotherapy regimens and upfront consolidation with autologous hematopoietic stem cell transplantation, although unfavorable outcomes such as primary refractory disease and early relapses are still common, except for the ALK1+ ALCL subgroup. Methodology: Hence, a multicenter, real-world, ambispective study was conducted, involving reference institutions in Brazil and two in the USA, to evaluate the main clinical-demographic characteristics associated with the outcomes of 179 patients diagnosed with nodal PTCL. Results and discussion: Individuals with nodal PTCL often presented at diagnosis with unfavorable clinical features, including a high frequency of advanced disease (stages III and IV), high tumor burden, poor performance status (ECOG ≥ 2 points), and frequent allocation in high-risk categories of the IPI and PIT prognostic indices. Patients with nodal PTCL included in this study globally exhibited low Complete Response rates, as well as shortened Overall Survival (OS) and Progression-Free Survival (PFS). In this cohort, we did not identify a robust survival benefit from the intensification of the CHOP regimen with the addition of etoposide (CHOEP protocol) or with BV-CHP. Age ≥ 60 years, ECOG ≥ 2, and lack of complete remission after primary therapy centered on CHOP-like chemotherapy were identified as independent prognostic factors associated with worse survival in this cohort represented by the four main histopathological subtypes of nodal PTCL. Conclusion: This analysis demonstrated a high frequency of unfavorable clinical features and poor OS and PFS outcomes in patients with nodal PTCL, regardless of the frontline chemotherapy regimen.