Innovative approaches for managing relapsed or refractory peripheral T-cell lymphoma

INTRODUCTION: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of hematologic malignancies arising from mature, post-thymic T- and natural killer (NK) cells. This review explores innovative approaches to managing relapsed or refractory PTCL, emphasizing the need for tailored treatment strategies given the generally poor prognosis associated with these entities. AREAS COVERED: Literature selection followed a comprehensive search of PubMed, MEDLINE and EMBASE up to 2026. The conventional frontline approach remains cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based chemotherapy. However, the addition of brentuximab vedotin (BV) has improved overall survival (OS) and progression-free survival (PFS) in specific subtypes, particularly anaplastic large cell lymphoma (ALCL). Despite these advances, most patients experience disease relapse or are primary refractory, highlighting a persistent unmet clinical need. Allogeneic stem cell transplantation (allo-SCT) offers curative potential for selected patients, but biological and logistical barriers constrain its wider application. EXPERT OPINION: These advances support a shift toward a more personalized management strategy, prioritizing immunotherapies, epigenetically directed therapies, and small-molecule inhibitors, tailored to disease subtype. By outlining current challenges and emerging treatment modalities, we aim to guide clinicians in optimizing care for this patient population.