Background: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of mature aggressive T-cell non-Hodgkin's lymphomas characterized by poor prognosis, which highlights the urgent need for novel therapeutic. The combination of gemcitabine, cisplatin and dexamethasone (GDP) is a recommended second-line treatment regimen according to lymphoma guidelines. Mitoxantrone hydrochloride liposome (Lipo-MIT), a nano-drug approved as the first treatment option for relapsed/refractory (r/r) PTCL, demonstrated certain efficacy and safety in a pivotal phase Ⅱ study (Cancer. 2025;e35672).

Aims: This prospective, single-arm, multicenter phase I/II study aims to investigate the safety and efficacy of combining Lipo-MIT with GDP regimen (MGDP) in patients (pts) with r/r PTCL. Preliminary interim results were presented at EHA 2025 PF963. Here, we report updated results.

Methods: Pts with r/r PTCL were recruited into this study, consisted of a 3+3 dose-escalation phase (Lipo-MIT at 12, 16, and 20 mg/m2 on day 1) and a specific dose-expansion phase (Lipo-MIT at the recommended phase II dose [RP2D], maximum 35 mg/cycle). Gemcitabine (1000 mg/m2), cisplatin (75 mg/m2), and dexamethasone (40 mg) were administered on day 1 of each 21-day cycle up to 6 cycles. The primary endpoints were to explore the RP2D of Lipo-MIT in phase I and the objective response rate (ORR) in phase II. Secondary endpoints included complete response (CR) rate, progression-free survival (PFS), overall survival (OS) and safety. This study has been registered (NCT05441761) at www.clinicaltrials.gov.

Results: At data cut-off on May 2025, 23 eligible pts (9 in phase I and 14 in phase II) were enrolled with a median age of 52 (range, 22-70) years. The subtypes included 15(65.2%) with PTCL-NOS, 5(21.7%) with angioimmunoblastic T-cell lymphoma (AITL), 1(4.3%) with ALK positive anaplastic large cell lymphoma (ALCL), 1(4.3%) with intestinal T-cell lymphoma (ITCL) and 1(4.3%) with nodal T-follicular helper (TFH) cell lymphoma. Most pts were primary refractory 19(82.6%). 21(91.3%) pts had advanced stage III /IV disease(Ann Arbor stage) and 13(56.5%) pts had IPI scores of 3-5. No dose-limiting toxicity (DLT) occurred in this phase I study and the RP2D of Lipo-MIT was established at 20 mg/m2. In phase II, the median Lipo-MIT dose per cycle was 18.7 (range, 16.5-20.2) mg/m2 with a median cycles of 4.5. The best ORR was 71.4% (10/14, 95% CI 41.9%-91.6%) with CR rate 42.9% (6/14, 95% CI 17.7%-71.1%) in the phase II cohort. For all evaluable pts (n=23), the best ORR and CR rate were 65.2% (15/23, 95% CI 42.7%-83.6%) and 39.1% (9/23, 95% CI 19.7%-61.5%), respectively. Moreover, promising activity was observed in pts of primary refractory, refractory to last prior therapy, high-risk (IPI 3-5) and high Ki67 expression (≥70%), with an best ORR of 68.4% (13/19), 66.7% (12/18), 69.2% (9/13) and 70.0%(7/10), respectively. At median follow-up of 10.4 months, the median PFS was 6.8 months, and median OS was 17.6 months. The common grade 3/4 treatment-related adverse events (TRAEs) were hematological toxicities, including neutropenia (65.2%), leucopenia (65.2%), anemia (39.1%) and thrombocytopenia (34.8%). Overall, safety in all pts was manageable in this study.

Conclusions: Lipo-MIT combined with GDP (MGDP) regimen demonstrated promising efficacy and manageable safety in r/r PTCL, warranting further investigation.

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2025
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