TP53 mutations identify high-risk events for peripheral T-cell lymphoma treated with CHOP-based chemotherapy.

Abstract

Nodal peripheral T-cell lymphomas (PTCL), the most common PTCLs, are generally treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based curative-intent chemotherapy. Recent molecular data have assisted in prognosticating these PTCLs, but most reports lack detailed baseline clinical characteristics and treatment courses. We retrospectively evaluated cases of PTCL treated with CHOP-based chemotherapy that had tumors sequenced by the Memorial Sloan Kettering Integrated Mutational Profiling of Actionable Cancer Targets next-generation sequencing panel to identify variables correlating with inferior survival. We identified 132 patients who met these criteria. Clinical factors correlating with an increased risk of progression (by multivariate analysis) included advanced-stage disease and bone marrow involvement. The only somatic genetic aberrancies correlating with inferior progression-free survival (PFS) were TP53 mutations and TP53/17p deletions. PFS remained inferior when stratifying by TP53 mutation status, with a median PFS of 4.5 months for PTCL with a TP53 mutation (n = 21) vs 10.5 months for PTCL without a TP53 mutation (n = 111). No TP53 aberrancy correlated with inferior overall survival (OS). Although rare (n = 9), CDKN2A-deleted PTCL correlated with inferior OS, with a median of 17.6 months vs 56.7 months for patients without CDKN2A deletions. This retrospective study suggests that patients with PTCL with TP53 mutations experience inferior PFS when treated with curative-intent chemotherapy, warranting prospective confirmation.

• Authors: William T Johnson, Nivetha Ganesan, Zachary D Epstein-Peterson, Alison J Moskowitz, Robert N Stuver, Catherine R Maccaro, Natasha Galasso, Tiffany Chang, Niloufer Khan, Umut Aypar, Natasha E Lewis, Andrew D Zelenetz, M Lia Palomba, Matthew J Matasar, Ariela Noy, Audrey M Hamilton, Paul Hamlin, Philip C Caron, David J Straus, Andrew M Intlekofer, Connie Lee Batlevi, Anita Kumar, Colette N Owens, Craig S Sauter, Lorenzo Falchi, Jennifer K Lue, Santosha A Vardhana, Gilles Salles, Ahmet Dogan, Nikolaus D Schultz, Maria E Arcila, Steven M Horwitz
• Journal: Blood advances (Blood Adv) Vol. 7 Issue 17 Pg. 5172-5186 (09 12 2023) ISSN: 2473-9537 [Electronic] United States
• PMID: 37078708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Topics

• Humans
• Lymphoma, T-Cell, Peripheral (drug therapy, genetics)
• Prognosis
• Retrospective Studies
• Prospective Studies
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Mutation