PRIMO phase II dose expansion final analysis: Duvelisib monotherapy in R/R PTCL

Final results from the dose expansion phase of the phase II, multicenter, open-label PRIMO trial (PRIMO-EP; NCT03372057), evaluating duvelisib monotherapy in adults with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL), were published in the Journal of Clinical Oncology by Mehta-Shah et al. PRIMO-EP enrolled 123 patients with histologically confirmed PTCL who had received ≥2 cycles of one standard regimen for PTCL. Following dose optimization results, patients received duvelisib 75 mg twice daily for 2 cycles, followed by 25 mg twice daily until progressive disease (PD) or unacceptable toxicity. The primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR).

Key data: The IRC-assessed ORR was 48.0% (95% confidence interval [CI], 39.1–56.8), with complete response (CR) in 33.3% of patients (95% CI, 25.0–41.7). Median time to response (TTR) was 1.8 months (range, 0.5–3.8), median duration of response (DoR) was 7.9 months (95% CI, 6.4–21.0), median IRC-assessed progression-free survival (PFS) was 3.4 months (95% CI, 1.8–3.9), and median overall survival (OS) was 12.4 months (95% CI, 8.4–22.7). In the angioimmunoblastic T-cell lymphoma (AITL) subgroup (n = 37), outcomes were notably improved (ORR, 62.2%; CR, 51.4%; median PFS, 8.3 months; median OS, 18.1 months). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 74.0% of patients; the most common were increased alanine aminotransferase (21.1%), decreased neutrophil count (17.9%), increased aspartate aminotransferase (17.1%), and diarrhea (9.8%).

Key learning: Duvelisib demonstrated clinically meaningful activity across R/R PTCL subtypes, with notable responses in AITL, and a manageable safety profile, supporting its consideration in this challenging setting and continued evaluation in T-follicular helper cell lymphoma.