Introduction: Extranodal NK/T-cell lymphoma (ENKTL), nasal type, is typically treated with chemoradiotherapy but often causes significant toxicity. PD-1 inhibitors, pembrolizumab and tislelizumab, have shown efficacy in relapsed or refractory ENKTL, although responses may vary with the tumor microenvironment (TME). Our previous reported analysis suggests that newly diagnosed ENKTL (ND-ENKTL) predominantly exhibit an immune-activated TME, which may enhance their response to PD-1 blockade (Mod Pathol. 2020 Apr;33(4):603-615).
Methods: This open-label, single-arm phase II trial enrolled stage I/II ND-ENKTL patients with low or low-intermediate PINK or PINK-E risk. Patients received tislelizumab (200 mg IV every 3 weeks) concurrently with radiotherapy (40 Gy/20 fractions), followed by tislelizumab maintenance for up to 2 years or until progression or toxicity. Tumor response was evaluated using CT or PET/CT, and AEs were graded by CTCAE v5.0.
Objectives: This study aims to evaluate the efficacy and safety of tislelizumab combined with radiotherapy as first-line therapy for limited-stage, low-risk ENKTL.
Results: As of May 2025, 24 patients were enrolled, and 19 were evaluable. Most (68.4%) were < 60 years, all ECOG 0-1, and 12 were EBV-DNA positive. The ORR and CR were 84.2% (n=16/19) after a median 7.2-month follow-up. Three patients developed extra-UADT progression (skin, GI, brain), but no local relapse occurred. Most AEs were documented as grade 1–2, and one grade 3 viral pneumonia occurred. Median PFS and OS have not yet been reached.
Conclusions: Tislelizumab combined with radiotherapy achieved high response rates with manageable toxicity, supporting it as a potentially safer, effective first-line treatment for limited-stage, low-risk ENKTL.
