Extranodal natural-killer/ T-cell lymphoma, nasal-type (ENKTL-NT) is an aggressive, angiocentric, and extensively necrotic malignancy, universally associated with Epstein-Barr virus (EBV) infection. Although highly prevalent in South America, few studies involving cohorts from this region have been published. Brazil is the largest and most populous country in South America, but Brazilian data on ENKTL-NT are extremely scare. In order to fill this gap, the current study aims to describe clinical and laboratory characteristics, assess clinical outcomes, determine predictors of survival and compare responses between different therapeutic modalities applied in a multicenter cohort of Brazilian patients with ENKTL-NT.

This is a retrospective, observational and multicenter study, involving 98 patients with ENKTL-NT diagnosed and treated at 20 different Brazilian institutions between January 2000 and December 2021. Endpoints included overall response rate (ORR), overall survival (OS) and progression-free survival (PFS). Survival curves were constructed using the Kaplan-Meier method and the Log-Rank test was used to assess the relationship between variables and outcomes. Univariate analysis was performed using the semi-parametric Cox test and multivariate analysis by Cox regression method or proportional ratios model.

The median age was 50 years (IqR 40-58) and 60.2% (59/ 98) were male. Sixty-three percent (62/ 98) had B-symptoms, 26.5% (26/ 98) had ECOG ≥ 2, 16.3% (16/ 98) had extranasal disease, 34.7% had advanced-stage III/ IV, and 30.2% (29/ 98) had high-risk PINK score. With a median follow-up of 49.0 months (95% CI: 35.8-62.3), the estimated 2-year OS and PFS were 51.1% (95% CI: 40.4-61.6) and 17.7% (95% CI: 4.5-30.8), respectively. Among early-stage disease (IE/ IIE) patients, the estimated 2-year OS were 81.3% (95% CI: 64.8-97.7) for SCRT (sequential chemoradiotherapy) followed by CHOP-like, 53.2% (95% CI: 29.3-77.1) for CCRT (concurrent chemoradiotherapy) followed by VIPD, and 50.5% (95% CI:21.4-79.5) for SCRT followed by asparaginase-based regimens, p = 0.221. CCRT-VIPD was associated with higher early-mortality (p = 0.034), and higher rates of neutropenia (p = 0.075), febrile neutropenia (p = 0.043) and mucositis (p < 0.001). Among advanced-stage (III/ IV) disease, the estimated 2-year OS were 37.0% (95% CI: 8.9-65.0) for asparaginase-based regimens and 33.0% (95% CI: 1.9-68.5) for anthracycline-based regimens, p = 0.851. Chemoradiotherapy (CRT) was associated with benefit for OS (p = 0.001) and PFS (p = 0.007) compared to chemotherapy alone. In multivariate analysis, anemia (HR 2.052, p = 0.038), lymphopenia [HR 3.600, p = 0.012], advanced- stage disease (III/ IV) [HR 3.101, p = 0.007], bone marrow infiltration [HR 5.406, p = 0.034] and omission of RT in up-front therapy [HR 2.791, p = 0.023] were independent factors associated with decreased survival.

High-dose EF-RT proved to be the cornerstone for the treatment of early-stage ENKTL-NT, and omission of this therapeutic modality was associated with decreased OS and PFS in Brazilian patients. In our real-life study, CCRT-VIPD regimen was poorly tolerated, and surprinsingly protocols based on anti-MDR agents were not associated with increased survival either in early- or advanced-stage disease. We also found that anemia, lymphopenia, advanced-stage (III/IV) and bone marrow involvement were independent predictors associated with poor clinical outcomes.