Favorable safety and efficacy of duvelisib maintenance after autologous stem cell transplant in peripheral T-cell lymphomas

Background Post-transplant relapse is the principal cause of treatment failure in peripheral T-cell lymphoma (PTCL) after autologous stem cell transplantation (ASCT), and no maintenance therapy is approved. We evaluated duvelisib, an oral dual phosphoinositide-3-kinase (PI3K)-δ/γ inhibitor, as post-ASCT maintenance. Methods In this single-center phase II trial (NCT04331119), patients aged 18–75 with PTCL or B-cell lymphoma began duvelisib approximately day +30 after ASCT for up to 11 cycles. After a safety lead-in with continuous dosing (25 mg twice daily, days 1–28; Schedule 1), subsequent patients received intermittent dosing (days 1–14 of a 28-day cycle; Schedule 2). The primary endpoint was 2-year progression-free survival (PFS) in patients with PTCL. Results Seventeen patients (12 PTCL, 5 B-cell lymphoma) received duvelisib; 15 were in complete remission at ASCT. Seven patients received Schedule 1 and ten received Schedule 2, with median treatment durations of 4.4 and 10.2 months, respectively. Grade ≥3 treatment-related adverse events occurred in nine patients, most commonly lymphopenia and transaminase elevation, and there were no treatment-related deaths. Three of seven patients on continuous dosing discontinued for toxicity. Among patients with PTCL, median follow-up was 46.4 months and estimated 2-year PFS was 74.1% (95% CI, 39.1–90.9%). Two-year overall survival among all patients was 94.1% (95% CI, 65.0–99.1%). Conclusions Duvelisib maintenance after ASCT is feasible, with a manageable safety profile, and intermittent dosing improved tolerability. Efficacy findings are exploratory and support evaluation in a larger randomized trial.