Introduction
Peripheral T-cell lymphomas (PTCL) are rare, heterogeneous, aggressive lymphomas. Current monotherapies have overall response rates (ORR) of <30% (except brentuximab vedotin for CD30+ ALCL). Duvelisib is an oral inhibitor of phosphatidylinositol 3-kinase-δ and -γ isoforms. PRIMO (NCT03372057) was a phase 2, open-label, single-arm trial that investigated duvelisib monotherapy in R/R PTCL. The use of duvelisib in PTCL is investigational.
Methods and Objectives
Following dose optimization, duvelisib 75 mg BID for 2 cycles (to maximize disease control), followed by 25 mg BID (to mitigate late toxicities) was administered until progressive disease (PD) or unacceptable toxicity. Primary endpoint: ORR by Independent Review Committee (Lugano 2014 criteria).
Results
PRIMO expansion phase (N=123) baseline characteristics: median age: 65 (range 21-92) years, median prior lines of therapy: 2 (range 1-9), most common histologies: PTCL-NOS (n=53), AITL (n=37), ALCL (n=20). Outcomes: ORR: 48%, complete response (CR): 33%, median progression-free survival (mPFS): 3.45 mo, median duration of response (DOR): 7.89 mo, mOS: 12.35 mo. (AITL subgroup: ORR: 62.2%, mPFS: 8.34 mo, mOS: 18.07 mo, mDOR: 11.70 mo).
There were 4 (3.3%) fatal treatment-related AEs, 6 (4.9%) fatal AEs (other than PD) which were unrelated/unlikely related to duvelisib, and 44.7% and 9.8% of AEs leading to dose hold and dose reduction, respectively.
Conclusions
PRIMO outcomes compare favorably to currently available single-agent options. AEs were generally manageable and consistent with those observed previously. Based on results in the AITL subgroup (T-follicular-helper cell-of-origin), the sponsor is initiating a randomized phase 3 study in the EU/UK to investigate duvelisib in R/R nodal T-follicular-helper cell lymphoma (TERZO™).
