TP53mutations identify high-risk events for peripheral T-cell lymphoma treated with CHOP-based chemotherapy

Author:

Johnson William T.12ORCID,Ganesan Nivetha1,Epstein-Peterson Zachary D.12ORCID,Moskowitz Alison J.12,Stuver Robert N.1ORCID,Maccaro Catherine R.1,Galasso Natasha1,Chang Tiffany1,Khan Niloufer12,Aypar Umut3ORCID,Lewis Natasha E.4ORCID,Zelenetz Andrew D.12ORCID,Palomba M. Lia12,Matasar Matthew J.12ORCID,Noy Ariela12ORCID,Hamilton Audrey M.12,Hamlin Paul12ORCID,Caron Philip C.12,Straus David J.12,Intlekofer Andrew M.125,Lee Batlevi Connie12ORCID,Kumar Anita12ORCID,Owens Colette N.12,Sauter Craig S.6,Falchi Lorenzo12,Lue Jennifer K.12,Vardhana Santosha A.125ORCID,Salles Gilles12ORCID,Dogan Ahmet4ORCID,Schultz Nikolaus D.7,Arcila Maria E.8,Horwitz Steven M.12

Affiliation:

1. 1Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY

2. 2Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY

3. 3Department of Pathology, Cytogenetics Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY

4. 4Department of Pathology, Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, NY

5. 5Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY

6. 6Department of Hematology and Oncology, Cleveland Clinic, Cleveland, OH

7. 7Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY

8. 8Department of Pathology, Molecular Diagnostic Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY

Abstract

AbstractNodal 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.

Publisher

American Society of Hematology

Subject

Hematology

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