Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of aggressive lymphomas. Primary nodal subtypes: PTCL-not otherwise specified, angioimmunoblastic TCL (AITL), and anaplastic large cell lymphoma. WHO classification of lymphoid neoplasms now groups AITL, PTCL-NOS with TFH phenotype, and follicular TCL under the category, "nodal T-follicular helper cell lymphoma" (nTFHL). This category is becoming the largest subgroup of nodal PTCL, with at least one-third of cases per conservative estimates now being categorized as nTFHL.
Duvelisib is an oral inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ/-γ isoforms. Approved indications: US and EU/UK for adult patients with relapsed/refractory CLL (and for SLL in the US) after ≥2 prior systemic therapies, and for refractory follicular lymphoma after ≥2 prior systemic therapies in the EU/UK.
PRIMO study (NCT03372057) outcomes of duvelisib in relapsed/refractory PTCL: objective response rate (ORR) 48.0%, median progression-free survival (mPFS) 3.45 mo, median overall survival (mOS) 12.35 mo. AITL subgroup outcomes: ORR 62.2%, mPFS 8.34 mo, mOS 18.07 mo.
The TERZO™ study (NCT06522737; EUCT: 2024-516605-23-00) is a multicenter, open-label, phase 3, randomized study evaluating duvelisib versus investigator's choice (gemcitabine or bendamustine) in patients with relapsed/refractory nTFHL. Primary endpoint: Independent Review Committee-assessed PFS. Key secondary endpoint: overall survival. Eligibility criteria: adults with relapsed/refractory nTFHL, ECOG performance status ≤2, and no prior history of allogeneic SCT or PI3K inhibitor use.
Duvelisib has demonstrated activity in relapsed/refractory PTCL, with more pronounced effect in AITL. TERZO will test the hypothesis that duvelisib monotherapy is associated with improved outcomes compared with gemcitabine or bendamustine in relapsed/refractory nTFHL.
