JCO Article Insights: Duvelisib in Patients with Relapsed or Refractory PTCL

Duvelisib, an oral PI3K inhibitor targeting gamma and delta isoforms, demonstrates significant efficacy in treating relapsed or refractory peripheral T-cell lymphoma (PTCL), particularly within the angioimmunoblastic (AITL) subtype. Final results from the Phase II PRIMO trial reveal an overall response rate of 48% and a 33% complete response rate, nearly doubling the performance of historical agents like HDAC inhibitors. While the drug serves as an effective bridge to curative stem cell transplantation for 15% of patients, long-term durability remains limited by a median progression-free survival of only four months. Safety data highlights frequent grade 3 or higher hepatotoxicity and neutropenia, leading a third of participants to discontinue treatment. Future clinical utility likely resides in all-oral combination therapies with JAK1 or EZH2 inhibitors to improve tolerability and deepen responses for non-transplant candidates.