Combined oral PI3Kδ inhibitor linperlisib and HDAC inhibitor chidamide in relapsed/refractory peripheral T-cell lymphoma: a multicenter phase 1 trial

This prospective, phase I trial evaluated the safety and efficacy of linperlisib plus chidamide in patients with relapsed/refractory peripheral T-cell lymphoma (r/r PTCL). Linperlisib was administered at three dose levels (40, 60, and 80 mg) following a standard "3 + 3" scheme. Fourteen patients were enrolled, including six with peripheral T-cell lymphoma, not otherwise specified and eight with nodal T-follicular helper lymphoma. No dose-limiting toxicities occurred. Linperlisib 80 mg daily was selected as the recommended phase II dose. The most common grade ≥3 adverse events were hematologic. Gastrointestinal toxicities improved with chidamide dose reduction. Among 14 efficacy-evaluable patients, the overall response rate was 64.3%, with a complete response rate (CRR) of 50.0%. With a median follow-up time of 13.0 months, median duration of response (DOR), progression-free survival, and overall survival (OS) were not reached. In conclusion, linperlisib plus chidamide demonstrated a favorable safety profile and encouraging preliminary efficacy in r/r PTCL.