The optimal treatment strategy for early-stage natural killer/T-cell lymphoma (NKTCL) remains unclear. This study aimed to evaluate and compare the clinical outcomes and adverse events (AEs) associated with two treatment regimens for early-stage NKTCL: pegaspargase with concurrent radiation therapy (P+CCRT) and pegaspargase, gemcitabine, and oxaliplatin (P-GEMOX) with sequential radiation therapy (SERT). Propensity score matching (PSM) was employed to ensure balanced comparison between these regimens.

We assessed the efficacy of P+CCRT from a phase II trial and P-GEMOX combined with SERT using real-world data. PSM was conducted at a 1:1 ratio with a caliper of 0.18 to align baseline characteristics between the treatment groups. Key outcomes analyzed included overall response rate (ORR), complete response rate (CR), progression-free survival (PFS), overall survival (OS), and AEs.

Following PSM, the study included 52 patients, with 26 in each treatment group. Baseline characteristics were balanced between the cohorts. The ORR for P+CCRT group was 100.0% compared to 88.5% for P-GEMOX+ SERT group, and the CR rates was 100.0% vs. 76.9%, respectively. The 3-year OS and PFS rates were both 92.3% for P+CCRT, while P-GEMOX showed 92.3% OS and 80.8% PFS. Adverse events, including hematological toxicity, hepatotoxicity, and coagulation dysfunction, were comparable between the two regimens.

P+CCRT is associated with comparable clinical outcomes compared to P-GEMOX + SERT in early-stage NKTCL, with comparable adverse events. Additionally, P+CCRT offers the benefit of a more streamlined treatment regimen with a shorter cycle. Given these encouraging results, further cohort studies are needed to validate these results.