Multicenter phase 1b-2 trial of liposomal mitoxantrone plus tislelizumab for relapsed or refractory ENKTL

Treatment options for relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) are limited. A multicenter phase 1b-2 trial in China evaluated the combination of lipisomal mitoxantrone (lipo-MIT) and tislelizumab (anti-PD-1) for R/R ENKTL. During dose escalation, patients received increasing doses of lipo-MIT combined with tislelizumab using a 3+3 design, followed by dose expansion at the recommended phase 2 dose (RP2D). The primary endpoint of the dose expansion phase was best complete response (CR) rate. Forty patients received study treatment (6 in dose escalation, 34 in dose expansion). No dose-limiting toxicities were observed, and the RP2D of lipo-MIT was 20 mg/m² every 4 weeks. The prespecified primary efficacy endpoint was met, with a CR rate of 53%(one-sided 95% lower CI bound 38%). The median progression-free survival was 8.2 months (95% CI 6.1-NE). The most common grade ≥ 3 adverse events were leukopenia (53%), neutropenia (40%), and febrile neutropenia (18%). The authors conclude that lipo-MIT plus tislelizumab showed promising antitumor activity with an acceptable safety profile in R/R ENKTL.