Efficacy of anti‐PD1 therapy in relapsed or refractory NK/T cell lymphoma: a matched cohort analysis from the LYSA

Extranodal NK/T cell lymphoma (ENKTCL) is a rare subset of peripheral T lymphoma of which Asparaginase containing regimens are the standard of care. Despite recent improvements in the therapeutic strategy, patient’s prognosis remains poor, especially for those who experienced relapsed or refractory (R/R) disease. Recent studies highlighted that immune escape mechanisms are involved in ENKTCL pathogenesis. Particularly, the frequent PD-L1 upregulation led to assess the efficacy of anti-PD1 (aPD1) therapy in small cohorts of R/R ENKTCL patients, with encouraging results. Our study aims to evaluate the efficacy of aPD1 therapy alone or in combination in 37 patients with R/R ENKTCL. We also performed a comparative analysis with a historic cohort of 38 patients treated for R/R ENKTCL before immunotherapy era. 37 patients from 24 French centers, with R/R ENKTCL treated with at least one cycle of aPD1 as salvage therapy between 2017 and 2022 were analyzed in this study. Among them, 12 were included in the prospective ACSE Unicancer study and received aPD1 as monotherapy. The historic cohort used for the comparative analysis was established from the ENKTCL national observatory and composed of 38 R/R ENKTCL patients who received at least one cycle of first salvage therapy without aPD1 between 2006 and 2019. All patients were treated with Asparaginase-containing regimen as frontline therapy. Patient characteristics were as follows: median age of 52 years (19–79), sex ratio M/F of 2/1, disseminated stage and high PINK score respectively in 57% and 41% of the cases. The overall response rate at the last follow-up was 40.5% in the aPD1 group. With a median follow-up time of 6.5 months for the whole cohort and 23.4 months for survivors, progression free survival and overall survival (OS) at 2 years were 22.4% and 50.2%. Among the 22 patients who experienced progression or relapse after aPD1 initiation, 14 patients (64%) received salvage therapy, mostly containing gemcitabine in association with immunotherapy continuation. This cohort was then compared to the historic cohort after matching on a propensity score. 23 patients in each group were included in this analysis. OS was significantly improved in patients treated with aPD1 as salvage therapy alone or in combination (48.4% versus 23.1%, p = 0011). We report here the largest cohort of R/R ENKTCL treated with aPD1. Our study confirms the efficacy of aPD1 therapy in R/R ENKTCL and highlights its superiority as compared to other types of salvage therapy used in this setting before immunotherapy era. Our results will prompt us to now prospectively evaluate the benefit of aPD1 therapy as first line therapy in patients with high risk disseminated stage of ENKTCL, in combination with chemotherapy agents able to enhance anti-tumor immunity. Encore Abstract - previously submitted to regional or national meetings (up to <1’000 attendees), EHA 2023 Keywords: Extranodal non-Hodgkin lymphoma, Immunotherapy No conflicts of interests pertinent to the abstract.