Liposomal mitoxantrone plus tislelizumab in patients with relapsed or refractory extranodal natural killer/T-cell lymphoma: a phase 1b/2 trial

Treatment options for relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) remain limited. In this phase 1b/2 trial (NCT05464433), we evaluated the safety and efficacy of liposomal mitoxantrone (Lipo-MIT) plus anti-PD-1 tislelizumab in this setting. During dose escalation, patients received Lipo-MIT (16 or 20 mg/m2) plus tislelizumab using a 3 + 3 design, followed by dose expansion at the recommended phase 2 dose (RP2D). The primary endpoint of the dose-escalation phase was dose-limiting toxicities (DLTs), which were assessed to determine the RP2D. The primary efficacy endpoint of the dose-expansion phase was the best complete response (CR) rate. Between July 23 2022 and November 28 2024, 40 patients received study treatment (dose-escalation, n = 6; dose-expansion, n = 34). No DLTs were observed and the RP2D of Lipo-MIT was 20 mg/m2. The prespecified primary efficacy endpoint was met, with a CR rate of 53% (21/40; one-sided 95% lower confidence bound, 38%). The median progression-free survival (secondary endpoint) was 8.2 months (95% confidence interval, 6.1-not estimable) after a median follow-up of 15.3 months. The most common grade ≥ 3 adverse events were leukopenia (53%), neutropenia (40%), and febrile neutropenia (18%). In conclusion, Lipo-MIT plus tislelizumab showed promising anti-tumor activity with an acceptable safety profile in R/R ENKTL. Responses to immune checkpoint inhibitors in patients with relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) remain limited. Here the authors report the results of a phase 1b/2 trial of liposomal mitoxantrone plus anti-PD-1 tislelizumab in patients with R/R ENKTL.