Novel agents and therapeutic advances in T cell lymphoma

Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of aggressive lymphomas with generally poor outcomes. CHOP or CHOP-like regimens have long been the standard frontline therapy; however, the addition of brentuximab vedotin has improved overall survival and established a new standard of care for CD30-positive PTCL. Despite this advance, the outcomes of relapsed or refractory (R/R) disease remain dismal. In recent years, multiple novel agents have been developed for the treatment of PTCL, particularly for R/R settings. Molecular profiling has refined disease classifications, identifying subtypes such as nodal T follicular helper (TFH) lymphoma, PTCL-GATA3, and PTCL-TBX21, which differ in their pathogenesis, prognosis, and potential therapeutic vulnerabilities. Epigenetic modulators, including histone deacetylase inhibitors and an EZH1/2 inhibitor, have demonstrated particularly high activity in TFH-derived subtypes, supporting the integration of biomarker-driven patient selection as a path toward precision medicine in PTCL. This review summarizes current insights into the genetic landscape, recent clinical advances in novel agents, and future perspectives on therapeutic stratification, highlighting the need to translate molecular insights into durable clinical benefits for patients with PTCL.