Treating relapsed/refractory mature T- and NK-cell neoplasms with tislelizumab: a multicenter open label phase 2 study.

Patients with relapsed/refractory (R/R) mature T- and NK-cell neoplasms lack effective treatments after failure of standard therapies. This phase 2 study evaluated the efficacy and safety of the PD-1 inhibitor tislelizumab in these patients. Seventy-seven patients were treated with tislelizumab 200 mg every 3 weeks. Twenty-two patients with extranodal NK-/T-cell lymphomas (ENKTLs) were enrolled in cohort 1; 44 patients with peripheral T-cell lymphoma (PTCL) were enrolled in cohort 2 (21 patients had PTCL not otherwise specified, 11 patients had angioimmunoblastic T-cell lymphoma, and 12 patients had anaplastic large cell lymphoma). Cohort 3 was comprised of 11 cutaneous T-cell lymphoma patients: 8 patients with mycosis fungoides (MF) and 3 with Sézary syndrome. Of the 77 patients, 76.6% had advanced-stage disease, 51.9% had refractory disease, and 49.4% received ≥3 prior systemic regimens. Promising efficacy was observed in cohort 3 (median follow-up [FU] 16.6 months; overall response rate [ORR] 45.5%; complete response [CR] 9.1%; median duration of response [DOR] 11.3 months; median progression-free survival [PFS] 16.8 months; median overall survival [OS] not reached). Modest efficacy was observed in cohort 1 (median FU 8.4 months; ORR 31.8%; CR 18.2%; median DOR not reached) and cohort 2 (median FU 9.3 months; ORR 20.5%; CR 9.1%; median DOR 8.2 months). Most treatment-related adverse events were grade 1 or 2, and the safety profile was consistent with the known safety profile of tislelizumab. In conclusion, tislelizumab was well tolerated, achieving modest efficacy in R/R mature T- and NK-cell neoplasms, with some long-lasting remissions. ClinicalTrials.gov registration: NCT03493451.