T-cell lymphoma secondary to checkpoint inhibitor (CPI) used for other malignancies.

Abstract

88 Background: Wartewig et al. (Nature 2017) proved in a preclinical mouse model that anti-PD1 therapy could cause T-cell lymphoma. T-cell lymphoma as an adverse event of CPIs has never been reported. A 75-year-old male with h/o urothelial carcinoma presented with lung metastasis of adenocarcinoma of unknown primary that showed PDL1 staining 5% of cells. Patient was treated with carboplatin & paclitaxel. For progressive disease, the patient received Pembrolizumab. After 4 cycles of CPI he developed lymphocytosis and lymphadenopathy and diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), with bone marrow (BM) involvement. Patient died before receiving any treatment for lymphoma. We hypothesized that CPI caused clonal expansion of T cells. Methods: We performed T-cell receptor (TCR) sequencing by Immunoseq assay in biopsy specimens. We queried FDA Adverse Events Reporting System (FAERS) and VigiBase databases for T-cell lymphoma/leukemia, PTCL, NOS, Mycosis Fungoides, Anaplastic Large & Cutaneous T-cell Lymphoma as an adverse event (AE) secondary to nivolumab, pembrolizumab or ipilimumab. Results: Through TCR sequencing we identified single clonal expansion before PD1 therapy in lung (0.008%) to 11% in bone marrow and 40% in lymph node (post treatment samples). Additional targeted exome sequencing of the lymphoma revealed a TET2 mutation. We conclude that anti-PD1 caused clonal expansion of the T cells harboring TET2 mutation leading to T-cell lymphoma. Findings of FARES and VigiBase review are shown in the Table. Conclusions: T-cell lymphoma is a rare complication of CPIs, with high mortality (20%). Long term follow up of patients receiving CPIs is needed. [Table: see text]