The AITL cell-of-origin, a T-follicular helper cell (TFH), has a set of mutations also found in some PTCL-NOS; this similarity has led to a reclassification (WHO 5th edition), grouping AITL, PTCL-NOS w/TFH phenotype, and follicular-T-cell lymphoma together as nodal TFH lymphoma (nTFHL).
Duvelisib is an oral inhibitor of phosphatidylinositol 3-kinase-δ and -γ. US indications: adults with R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after ≥2 prior lines of systemic therapy. US Limitations of Use: Duvelisib is not indicated or recommended for the treatment of any patients with CLL/SLL as initial or second line treatment due to increased risk of treatment-related mortality. EU/UK indications: adults with R/R CLL after ≥2 prior therapies and for follicular lymphoma that is refractory to ≥2 prior systemic therapies. The use of duvelisib in PTCL is investigational.
In the phase 2 PRIMO study (NCT03372057), duvelisib in R/R PTCL demonstrated an overall response rate (ORR) of 48.0%, median progression free survival (mPFS) of 3.45 mo, and median overall survival (mOS) of 12.35 mo. Notably, AITL subgroup outcomes were ORR 62.2%, mPFS 8.34 mo, mOS 18.07 mo.
Accordingly, the phase 3 TERZO™ study (NCT06522737; EUCT:2024-516605-23-00) will evaluate efficacy and safety of duvelisib versus investigators' choice of gemcitabine or bendamustine in ~124 EU/UK patients with R/R nTFHL. Primary outcome: PFS; key secondary outcome: OS.
Duvelisib has demonstrated activity in R/R PTCL, with more pronounced effects in AITL (TFH cell-of-origin). TERZO will test the hypothesis that duvelisib is associated with improved outcomes versus gemcitabine or bendamustine in R/R nTFHL.
