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Pembrolizumab + decitabine + pralatrexate is an investigational combination therapy being evaluated in the Phase Ib EMBOLDEN trial (NCT03240211) for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Pembrolizumab is a humanized monoclonal antibody that functions as a checkpoint inhibitor by binding to the programmed death-1 (PD-1) receptor, thereby preventing interaction with its ligands (PD-L1 and PD-L2) and restoring T-cell mediated anti-tumor activity. Decitabine is a hypomethylating agent that inhibits DNA methyltransferase, potentially reversing epigenetic silencing of genes involved in tumor suppression and immune recognition. Pralatrexate is an antifolate that competitively inhibits dihydrofolate reductase (DHFR), disrupting DNA synthesis in malignant cells. This multi-arm study, sponsored by the University of Virginia with support from Merck, aims to determine the safety and efficacy of these agents in combination for heavily pretreated patients.
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