Efficacy and safety of duvelisib combined with chidamide as first-line treatment for angioimmunoblastic T-cell lymphoma (AITL)

Abstract

Abstract Background: Angioimmunoblastic T-cell lymphoma (AITL), an aggressive peripheral T-cell lymphoma (PTCL) subtype, demonstrates limited responsiveness to conventional chemotherapy, with a 5-year overall survival (OS) of 44% and progression-free survival (PFS) of 32%. Duvelisib (DUV), an oral dual inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ/γ isoforms, has shown promising efficacy and tolerability in relapsed/refractory PTCL. This study evaluates the efficacy and safety of combining duvelisib with chidamide as first-line therapy for AITL to explore optimized treatment strategies. Methods: This study was a prospective, single arm study (NCT05976997) that enrolled newly diagnosed AITL patients aged ≥18 years. All patients received duvelisib plus chidamide combined with CHOP chemotherapy of 6 cycles (Q3W). The dosing schedule is as follows:duvelisib 25mg (bid) for 10 days, and chidamide 20mg (biw).The primary endpoint was safety after induction. Secondary endpoints included duration of response (DoR), overall response rate (ORR), complete response (CR),progression-free survival (PFS), and overall survival (OS). Adverse events were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: From ‌November 3, 2022 to June 11, 2024, a total of 12 newly diagnosed AITL were enrolled. The median age of all patients was 63 years (range 47-69), 58.3% were male. Among all patients, 91.7% were advanced stages disease with stage IV and 8 (66.7%) patients had IPI scores of 3–4. And 6 patients (50%) presented with B symptoms. As of the data cutoff, 12 patients were evaluated for efficacy,the ORR was 75% (9/12) and the CR rate was 66.7% (8/12).With a median follow-up of 16.54 months (range 7.20–24.93), the median PFS and OS have not yet been reached. the 1-year PFS and OS rates were 90% and 100%,respectively.The common grade 3/4 treatment-related adverse events (TRAEs) (incidence≥10%) were mainly hematological toxicity, including leucopenia (41.7%)and neutropenia (41.7%), as well as infections including lung infections （33.3%）. Conclusions: The preliminary results of the study indicate that the combination of targeted therapy using DUV and chidamide and chemotherapy shows good efficacy and manageable safety. profile in newly diagnosed AITL, warranting further exploration.