AbstractBackgroundNasal‐type extranodal natural killer (NK)/T cell lymphoma (ENKTL) is a rare and aggressive type of lymphoma. The optimal chemotherapy regimen for ENKTL has not yet been established. In this study, we compared the LVDP (L‐asparaginase, etoposide, dexamethasone, and cisplatin) and GLIDE (gemcitabine, L‐asparaginase, ifosfamide, dexamethasone, and etoposide) chemotherapy regimens for the treatment of ENKTL.MethodsA total of 267 patients with newly diagnosed ENKTL were included in this retrospective study. Propensity score matching (PSM) was used to adjust for confounders between the LVDP and GLIDE groups. Treatment responses, survival outcomes, and toxicities between the two groups were compared before and after PSM.ResultsAt the end of therapy, the objective response rate (ORR) and complete response (CR) were 83.5% and 62.2%, respectively, for all patients. The ORR and CR were 85.5% and 62.2% for the LVDP group compared with 79.3% and 62.2% for the GLIDE group, respectively, and no differences between the two groups were found (ORR,p= 0.212; CR,p= 0.996). With a median 71 months follow‐up, the 5‐year progression‐free survival (PFS) and overall survival (OS) rates were 64.3% and 68.5%, respectively. The 5‐year PFS and OS were 65.6% and 70.1% for the LVDP group compared with 61.6% and 64.6% for the GLIDE group, respectively (PFS,p= 0.478; OS,p= 0162). After PSM, no significant differences in short‐term efficacy (ORR,p= 0.696; CR,p= 0.264) or long‐term efficacy (PFS,p= 0.794; OS,p= 0.867) between the two groups were identified. However, treatment‐related toxicities were milder in the LVDP group compared to the GLIDE group, even after adjusting for confounders via PSM.ConclusionIn conclusion, both LVDP and GLIDE regimens are effective for the treatment of ENKTL. However, the LVDP regimen is safer than the GLIDE regimen, with milder treatment‐related toxicities. Therefore, the LVDP regimen could be a preferable option for patients with ENKTL.