Combination of Mitoxantrone Hydrochloride Liposome with Gemcitabine, Cisplatin and Dexamethasone in Patients with Relapsed or Refractory Peripheral T Cell Lymphoma: A Phase I Study

Background : Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of mature aggressive T-cell non-Hodgkin's lymphomas characterized by poor prognosis, highlighting the urgent need for novel therapeutic strategies. The combination of gemcitabine, cisplatin and dexamethasone (GDP) is recommended as the second-line treatment regimen according to lymphoma guidelines. Mitoxantrone hydrochloride liposome (Lipo-MIT) is a nano-drug that has been approved as the first treatment option for relapsed/refractory (r/r) PTCL, and has shown certain efficacy and safety in a pivotal phase Ⅱ study. This study aims to investigate the safety and efficacy of combining Lipo-MIT with GDP regimen (MGDP) in patients (pts) with r/r PTCL (NCT05441761). Methods: Pts with r/r PTCL were recruited in this prospective, multicenter, open-label phase I study with a 3+3 dose-escalation design. Lipo-MIT was administered at three dose levels (DL1: 12 mg/m2, DL2: 16 mg/m2, DL3: 20 mg/m2, d1). Gemcitabine was given at 1000 mg/m2, cisplatin at 75 mg/m2, and dexamethasone at 40 mg on day 1 of each cycle (Q3W), and up to 6 cycles of therapy were planned. The primary endpoint is to explore the recommended phase II dose (RP2D) of Lipo-MIT. Secondary endpoints were to assess the tolerability (i.e. dose-limiting toxicity (DLT)), complete response (CR) rate, objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. Results: At data cut-off on 17 July 2024, 9 eligible pts (DL1: n=3, DL2: n=3, DL3: n=3) were enrolled including 3 with angioimmunoblastic T-cell lymphoma (AITL), 5 with PTCL-NOS and 1 with ALK positive anaplastic large cell lymphoma (ALCL). Among them, 6 cases (66.7%) were refractory pts. The median age of all pts is 46 (range, 31-70) years, and 4 pts (44.4%) were IPI score 3-5. 8 pts (88.9%) had advanced stage III or IV (Ann Arbor stage). No DLT occurred in this phase I study. And the RP2D was 20 mg/m2 for Lipo-MIT. The CR rate and ORR were 33.3% (3/9, 95% CI 7.5%-70.1%) and 55.6% (5/9, 95% CI 21.2%-86.3%), respectively. Besides, in refractory pts, the CR rate was 33.3% (2/6) and ORR rate was 66.7% (4/6). With a median follow-up of 5.1 (range, 0.03-20.2) months currently, the median PFS and OS will be reported after long-term follow-up. The common grade 3/4 Treatment-related adverse events (TRAEs) were mainly hematological toxicity, including neutropenia (66.7%), leucopenia (44.4%), anaemia (33.3%) and thrombocytopenia (11.1%). Overall, safety in all pts was tolerable during this study. Conclusions: Lipo-MIT plus GDP (MGDP) regimen proves an promising efficacy in r/r PTCL pts with manageable safety profiles. A phase II, multi-center, single-arm study is ongoing to confirm and validate the findings from this study.