Liposomal Mitoxantrone Monotherapy in Patients with Relapsed or Refractory Mature T-cell and Natural Killer-cell Neoplasms: A Phase 2, Multicenter, Open-label, Single-arm Trial

Introduction: The prognosis of relapsed or refractory mature T- and natural killer (NK)-cell lymphoma remains dismal. Novel agents are urgently needed to improve the outcomes for this population.

Methods: In this phase 2, multicenter, open-label, single-arm study (NCT03776279), the authors report the efficacy and safety of liposomal mitoxantrone (Lipo-MIT) monotherapy in patients with relapsed or refractory mature T- and NK-cell lymphoma. Lipo-MIT was administered intravenously at 20 mg/m once every 4 weeks. The primary end points were the objective response rate (ORR) determined by the independent review committee (IRC) and investigators. Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.

Results: From April 26, 2018, to August 10, 2022, 108 eligible patients were enrolled and treated at 26 study centers in China. The ORRs were 41.7% (95% confidence interval [CI], 32.3-51.5%) per IRC and 46.3% (95% CI, 36.7%-56.2%) per investigators; 25 (23.1%) and 15 (13.9%) patients, respectively, achieved complete response. With a median follow-up of 29.5 months, median PFS per IRC was 8.5 months (95% CI, 6.0-11.9); median OS was 23.3 months (95% CI, 12.0-not evaluable); median DoR per IRC was not reached. The most frequent treatment-emergent adverse events were decreased white blood cell count (75, 69.4%), decreased neutrophil count (73, 67.6%), and decreased platelet count (47, 43.5%).

Conclusions: Lipo-MIT monotherapy showed robust and durable antitumor activity with a manageable safety profile, representing a new therapeutic option in relapsed or refractory mature T- and NK-cell lymphoma.