Introduction
Peripheral T-cell lymphomas (PTCL) are a group of aggressive lymphomas. Duvelisib is an oral dual inhibitor of phosphatidylinositol 3-kinase-δ/γ, with activity in PTCL. The duvelisib dosing regimen in PTCL was established in PRIMO (NCT03372057), a phase 2, open-label, single-arm study.
Methods
PRIMO enrolled patients with relapsed/refractory PTCL. PRIMO expansion phase (PRIMO-EP) dose: duvelisib 75mg BID for 2 cycles to maximize early disease control, followed by 25mg BID to mitigate late toxicities, continued until progressive disease/unacceptable toxicity. Here we report impact of prior treatments and expanded safety analyses from PRIMO-EP.
Results
Baseline histologies (N=123): PTCL-not otherwise specified (n=53), angioimmunoblastic TCL (AITL) (n=37), anaplastic large cell lymphoma (n=20). Efficacy outcomes: ORR 48%, complete response (CR) 33%, median duration of response (mDOR) 7.9 mos, median progression-free survival (mPFS) 3.4 mos, mOS 12.4 mos. AITL subgroup: ORR 62%, CR 51%, mDOR 11.7 mos, mPFS 8.3 mos, mOS 18.1 mos.
ORR by prior therapies: 1 (n=34) ORR=29.4%; 2, (n=29), ORR=65.5%; ≥3, (n=59), ORR=49.2%. 123 patients had a treatment period ≤2 cycles, 63 had >2-6 cycles, 25 had >6 cycles. Adverse events (AEs) in ≥20% of patients (cycles ≤2/cycles >2-6/ cycles >6) included: neutropenia (29%/22%/16%), aspartate/alanine aminotransferase increased (25-29%/29-35%/4%), thrombocytopenia (19%/13%/28%), fatigue (15%/13%/24%), diarrhea (20%/25%/32%).
Conclusions
Duvelisib efficacy outcomes did not show consistent patterns based on number of prior lines, and no consistent patterns of higher rates of persisting/emerging AEs with longer duvelisib treatment. Based on AITL subgroup efficacy, the sponsor has initiated the randomized, phase 3 TERZO™ study investigating duvelisib in relapsed/refractory nodal T-follicular helper cell lymphoma (NCT06522737).
