Extranodal NK/T-Cell Lymphoma in Latin America: A Retrospective Multinational Analysis of Clinical Features, Therapeutic Approaches and Outcomes from the Latin American Group of Lymphoproliferative Disorders (GELL)
Authors: Valvert Fabiola , Fernandez Vargas Omar Eduardo , Paredes Sally , Lage Luís Alberto de Pádua Covas , Villela Martinez Luis Mario , Macias Abasto Jose Marcial , Irigoin Victoria , Carias Alvado Cesar Camilo , Barrios Juan C , Acosta Maldonado Brenda Lizeth , Castro Denisse , Ramos Condori Betty , Pereira Juliana , Rivas-Vera Silvia , Beltran Brady , Malpica Luis 
Published: December 2024

Background

Extranodal NK/T-cell lymphoma (ENKTL) is a rare subtype of Epstein-Barr virus (EBV)-related non-Hodgkin lymphoma. It has a distinct geographic and ethnic predilection, being more common in East Asia and Latin America (LATAM). ENKTL is known for its poor prognosis, largely due to its aggressive nature and the frequent development of resistance to conventional chemotherapies. However, the introduction of asparaginase-based regimens combined with radiotherapy has led to improved outcomes in recent years. Despite these advances, there is no established standard of care, especially in resource-limited settings like LATAM. This study aims to fill the knowledge gap regarding ENKTL in LATAM, by analyzing the clinical features, therapeutic approaches, and outcomes of patients (pts) with ENKTL in this region.

Methods

A retrospective, multicenter study was conducted including pts aged ≥18 with newly diagnosed ENKTL from Guatemala (n=92), Mexico (n=87), Brazil (n=92), Peru (n=19), Bolivia (n=12) and Uruguay (n=1) from 2000 to 2023. Baseline demographics, clinical-biological disease characteristics, treatment patterns, and outcomes were collected and analyzed. Primary endpoint was overall survival (OS) defined as time from diagnosis to death from any cause. Kaplan-Meier method and Log-rank tests were used to estimate and compare survival probabilities.

Results

A total of 303 pts were included, with a median age at diagnosis of 44 years (18-86) and a male predominance (59.41%). Localized disease (stage I/II) was seen in 59% (n=180) and advanced (stage III/IV) in 41% of pts by TNM. Clinically, pts are commonly presented with visible ulcerative lesions (53.5%) or palate perforation (31.3%). B symptoms were seen in 57.8%, high LDH in 42.9%, bulky disease (&gt;7 cm) in 16.7% and hemophagocytic lymphohistiocytosis in 15.8%. Most pts (88.4%, n=268) received first line therapy, including concurrent or sequential radiotherapy plus chemotherapy (68%), radiotherapy alone (6%) and chemotherapy alone (26%). Among those managed with systemic chemotherapy (with or without radiation therapy), 28% (n=71/251) were treated with anthracycline- (i.e. CHOP); 13% (n=33/251) with platinum; 36% (n=90/251) with asparaginase; and 23% (n=57/251) with other regimens.

Complete response rates were seen in 38.6% of pts treated anthracycline- (47.7% localized vs 22.2% advanced); 66.7% with platinum-; (66.7% localized vs 64.3% advanced) and 48.9% with asparaginase-based regimens (63.3% localized vs 34.1% advanced). Responses were significantly better for platinum- (p=0.019) and worse for anthracycline-based therapy (p=0.02) in pts with advanced stage. No differences in responses by therapy regimens were seen in pts with localized disease.

Median follow up was reached at 12 months and 1-year OS of 59.4%. Worse OS was seen in pts with advanced vs early stage 6 months vs 28 months respectively; (p=0,001, HR 2,73, 95% CI 1.9-3.9), indistinctive of the type of treatment. Pts with early stage disease had a median OS of 38.6, 36.6 and 26.7 months for asparaginase-, anthracycline- and platinum-based treatments, respectively. Less favorable results were seen for advanced stages with median OS of 13.8, 9.8 and 17.6 months, respectively. The leading causes of death were progression (17%, n=52), infection (10%, n=29) and lack of access for treatment (7%, n=22).

Conclusion

This multicenter study represents one of the largest analyses of ENKTL in LATAM, providing valuable insights into the clinical, treatment patterns and outcome of this aggressive malignancy. Our findings highlight the poor prognosis associated with advanced-stage disease, irrespective of treatment regimen, underscoring the need for early detection and timely intervention. While asparaginase-based therapies showed promise in localized disease, outcomes for advanced stages remain suboptimal, emphasizing the limitations of current treatment strategies in resource-limited settings. The study also reveals significant barriers to care, including limited access to effective therapy, which contributes to the high mortality rate from disease progression and infections. These results underscore the urgent need for improved healthcare infrastructure and tailored therapeutic approaches to enhance outcomes for ENKTL pts in LATAM.