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

Nodal peripheral T-cell lymphomas (PTCL), the most common PTCLs, are generally treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-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 (MSK-IMPACT) next-generation sequencing (NGS) panel to identify variables correlating with inferior survival. We identified 132 patients who met these criteria. Clinical factors correlating with increased risk of progression (by multivariate analysis) were advanced-stage disease (HR, 5.1; 95% CI, 1.1-22.5, P=.03) and bone marrow involvement (HR, 3.0; 95% CI, 1.1-8.4; P=.04). The only somatic genetic aberrancies correlating with inferior progression-free survival (PFS) were TP53 mutations (HR, 3.1; 95% CI, 1.4-6.8; P=.005) and TP53/17p deletions (HR, 4.1; 95% CI, 1.1-15.0, P=.03). PFS remained inferior when stratifying by TP53 mutation status, with a median PFS of 4.5 months (95% CI, 3.8-13.9) for PTCL with a TP53 mutation (n=21) vs 10.5 months (95% CI, 7.8-18.1; P<.001) for PTCL without a TP53 mutation (n=111). No TP53 aberrancy correlated with inferior overall survival (OS). Though rare (n=9), CDKN2A-deleted PTCL correlated with inferior OS, with a median of 17.6 months (95% CI, 12.8-NR) vs 56.7 months (95% CI, 44.6-101.0; P=.004) for patients without CDKN2A deletions. This retrospective study suggests patients with PTCL with TP53 mutations experience inferior PFS when treated with curative-intent chemotherapy, warranting prospective confirmation.