Are CHOP-Plus Really CHOP-Minus Propositions in the Treatment of PTCL? A Comprehensive Assessment of the Strategy

Peripheral T-cell lymphomas (PTCLs) are a rare, heterogeneous subset of non-Hodgkin lymphomas (NHL) that are biologically and clinically distinct from B-cell lymphomas. They are typically resistant to chemotherapy and associated with poor outcomes compared to most B-cell malignancies. Despite this, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like regimens remain the standard frontline therapy-even though pivotal studies establishing CHOP in NHL included only B-cell patients, with no evidence for PTCL. For decades, efforts to improve outcomes have focused on "CHOP-plus" strategies, adding novel agents to the backbone. Outside of anaplastic large cell lymphoma (ALCL), where brentuximab vedotin has improved survival, this approach has generally failed; in most PTCL subtypes, 5-drug regimens add toxicity without clear benefit. After two decades of disappointing results, this review critically examines the evidence, the limitations of current strategies, and opportunities to rethink future approaches.