Combination of mitoxantrone hydrochloride liposome with chidamide in patients with relapsed or refractory peripheral T cell lymphoma: Updated results of the phase II study

Abstract Background Relapsed or refractory (R/R) peripheral T cell lymphoma (PTCL) is an aggressive and heterogeneous malignancy without standard treatment. Either mitoxantrone hydrochloride liposome (Lipo-MIT) monotherapy or chidamide (CHI) monotherapy has shown promising efficacy and favorable safety in R/R PTCL. This single-arm, prospective phase I/II study (NCT05527275) presented the primary safety and efficacy results from previous phase I cohort and preliminary efficacy and safety results from the phase II cohort at the 2024 European Society for Medical Oncology Annual Congress (ESMO 2024, abstract 810MO). Here, we report the updated results of phase II. Methods: Eligible patients were aged 18 years or older with R/R PTCL. Patients received the Lipo-MIT-CHI regimen once every 4 weeks for up to 6 cycles. Lipo-MIT was administered at 20 mg/m^2 (Recommended phase II dose) on day 1. CHI was administered at 20 mg twice weekly. The primary endpoint was the objective response rate (ORR). Key secondary endpoints were complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and safety. Results: At data cut-off on May 2025,28 eligible patients from phase II were enrolled including 15 (53.6%) refractory PTCL and 13 (46.4%) relapsed PTCL(first relapsed, n=10; at least two relapsed, n=3). The median age was 55 years old (range 25-68), and 64.3% of patients were male. Among them, 20 (71.4%) patients had stage III or IV (Lugano classification) and 8 (28.6%) patients had IPI scores of 3-5. In all evaluable patients, the ORR and CRR were 70.8% (17/24, 95% CI 48.9%-87.4%) and 45.8% (11/24, 95% CI 25.6%-67.2%), respectively. With a median follow-up duration of 5.3 months (range 0.03-15.1), the median PFS was 13.5 months, while the median OS was not reached. The Kaplan-Meier estimated 1-year PFS rate was 67.0% and 1-year OS rate was 79.1%. The common grade 3/4 treatment-related adverse events (TRAEs) were mainly hematological toxicity, including lymphocytopenia (53.6%), leucopenia (53.6%), neutropenia (46.4%), and thrombocytopenia (28.6%). Conclusions: The Lipo-MIT-CHI regimen showed a promising efficacy and manageable safety in patients with R/R PTCL.