Treatment patterns and survival outcomes after immunotherapy failure in patients with NK/T cell lymphoma: A multicenter retrospective study

Abstract Background: Natural killer/T cell lymphoma (NKTCL) is a distinct subtype of non-Hodgkin lymphoma, with a higher incidence in East Asia and South America. Immunotherapy-based regimens have been widely used in NKTCL as both first-line and salvage treatment. The patients' characteristics, post-immunotherapy treatment and prognostic data are limited for patients who experience disease progression after immunotherapy. Methods This multicenter retrospective study included NKTCL patients who progressed after immunotherapy between 2018 and 2024 from 6 medical centers in China. Post-progression overall survival (OS-2) was defined as the time from disease progression to immunotherapy to death from any cause. Post-progression progression-free survival (PFS-2) was defined as the time from disease progression to immunotherapy to disease progression to subsequent treatment or death. Survival data were analyzed using Kaplan-Meier method. Independent prognostic factors were analyzed using the Cox regression models. Results A total of 186 patients who progressed after immunotherapy were included in this study. Among them, 69 patients relapsed after an initial response to immunotherapy, while 117 patients had refractory disease. Ninety-two patients (49.1%) received immunotherapy-based regimen as the first-line treatment. After immunotherapy failure, 160 patients (86%) received subsequent treatment and 84 patients (45.2%) restarted immunotherapy. There were 27 patients developed hemophagocytic lymphohistiocytosis (HLH). The best overall response of post-immunotherapy treatment was 31.6%. The median OS-2 was 12.4 months (95% CI:10.0–15.4), and the median PFS-2 was 6.0 months (95% CI:4.3–11.7). Patients who restarted immunotherapy after progression had significantly improved OS-2 (16.5 vs. 9.5 months, P=0.0056) and PFS-2 (6.3 vs. 4.1 months, P=0.0330). Those with relapsed disease had better OS-2 than primarily refractory patients (16.5 vs. 10.4 months, P=0.0300). Multivariate analysis identified ECOG ≥2 (HR=2.54, 95% CI: 1.25–5.16), non-nasal type (HR = 2.38, 95% CI: 1.18–4.76) and CD4/CD8 ratio >2.6 (HR=3.02, 95% CI: 1.16–7.84) as adverse prognostic factors for OS-2, while immunotherapy retreatment was associated with improved survival outcomes (HR=0.27, 95% CI: 0.13–0.56). Conclusion Patients with NKTCL who failed immunotherapy had poor survival outcomes, and patients may still benefit from immunotherapy retreatment. Patients with higher ECOG-PS score, non-nasal type disease and higher CD4/CD8 ratio at immunotherapy failure had inferior survival outcomes.