The Clinical Features and Survival Outcome of 107 Newly Diagnosed Advanced Stage Extranodal NK/T-Cell Lymphoma Cases: A Triple-Center Study

Abstract

Objective Advanced stage extranodal natural killer/T-cell lymphoma (ENKTL) is a distinct type of non-Hodgkin lymphoma and the prognosis of ENKTL is poor with current treatment. This study aimed to investigate the clinical features, treatment strategy and survival outcome in patients with advanced stage ENKTL. Patients and Methods A total of 107 patients with newly diagnosed advanced stage ENKTL between January 2010 and December 2014 were reviewed from three cancer centers. Survival probability was calculated using Kaplan-Meier and the survival curves were compared by Log rank test. Cox regression analyses was performed to investigate the prognostic factors in ENKTL. Results The median patient age in our cohort was 42.0 years, with a male to female ratio of around 2.3:1. Over half of the patients had B symptoms (n = 61), high IPI scores (≥ 2, n = 60) and high Prognostic Index of Natural Killer Lymphoma (PINK) scores (≥ 3, n = 69). Elevated LDH level was present in around half of the patients (44/91). Most patients (n = 88) in our cohort originated in upper aerodigestive tract and the remaining 19 cases presented with non-upper aerodigestive tract involvement at first diagnosis. Chemotherapy regimens used in our study mainly include CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (n = 26), L-asparaginase (L-asp) containing chemotherapy (GELOXD (gemcitabine, l-asparaginase, oxaliplatin and dexamethasone) and SMILE (L-asparaginase, methotrexate, ifosfamide, etoposide, and dexamethasone)) (n = 66). No significant difference between the baseline clinical characteristics was found between the L-asp and CHOP group. The CR rate after treatment was 39.3% (42/107) for the whole cohort. The 3-year progression-free survival (PFS) and 3-year overall survival (OS) rate was 41.0% and 41.5%, respectively. The 3-year PFS (49.2% vs 26.5%, P = 0.048) and 3-year OS (49.4% vs 26.0%, P = 0.030) was significantly higher in the L-asp group than the CHOP group. Patient CR status and PINK score were proved to be significant independent factors affecting OS and PFS by multivariate analysis. The grade 3/4 hematologic toxicity (P = 0.0003) and non-hematologic toxicity (P = 0.0002) occurred more frequently in the SMILE group than the GELOXD group. Conclusion Our results demonstrated that L-asp containing chemotherapy could provide favorable survival outcomes in patients with advanced stage ENKTL.

Efficacy of Frontline Chemotherapy for Extranodal Natural Killer/T-Cell Lymphoma: A Systematic Review and Network Meta-Analysis

“…Survival outcomes in the large multicenter studies were similar to that of prospective phase 1/2 trials (3-year OS, 66-87.5%; 5-year OS, 60-82.1%) and retrospective studies (about 75%) in the early-stage ENKTCL [ 10 , 11 , 20 , 23 , 26 , 37 , 48 , 49 , 53 , 54 , 56 - 58 ]. Furthermore, the survival benefits of ASP/GEM-based regimens were prominent/substantial in advanced stage patients [ 9 , 18 , 37 ]. Consistent with the randomized controlled trial study [ 18 ], even compared with SMILE, one of the best-studied regimens, ASP/GEM-based regimens still resulted in superior outcomes.…”

“…According to the inclusion criteria, a total of 10 studies published between 2013 and 2022 were identified for the chemotherapy regimens review of ENKTCL [9,18,[35][36][37][38][39][40][41][42]. The article inclusion and exclusion procedures are demonstrated in a consort flow diagram of study selection (Fig.…”

“…More than 70% of patients present with local disease generally managed with combined modality therapy involving irradiation and chemotherapy, while advanced-stage disease is mainly treated with systemic chemotherapy [6][7][8]. However, the 2-year overall survival (OS) rate of advanced ENKTCL was only about 30.0% in the era of anthracycline (ANT)-based chemotherapy [9][10][11][12][13].…”

Real‐World clinical features and survival outcomes associated with primary gastrointestinal natural killer/T‐cell lymphoma from 1999 to 2020

“… 7 , 8 For advanced‐stage ENKTL, asparaginase‐containing chemotherapy is frequently administered, resulting in a 3‐year PFS rate of 49.2% and a 3‐year OS rate of 33%–49.4%. 9 , 10 Currently, there is no standard treatment strategy for PGINKTL, clinicians often refer to treatment for ENKTL, nasal type, and surgery for some patients; however, their value for treating PGINKTL remains unknown. Conversely, the survival outcomes of gastrointestinal NK/T‐cell lymphoma (GINKTL) seemed significantly worse than those of UAT‐ENKTL.…”

“…Radiotherapy combined with asparaginase‐containing chemotherapy is an established paradigm for early‐stage ENKTL treatment, resulting in 5‐year progression‐free survival (PFS) and overall survival (OS) rates of 64%–83% and 64%–89%, respectively 7,8 . For advanced‐stage ENKTL, asparaginase‐containing chemotherapy is frequently administered, resulting in a 3‐year PFS rate of 49.2% and a 3‐year OS rate of 33%–49.4% 9,10 . Currently, there is no standard treatment strategy for PGINKTL, clinicians often refer to treatment for ENKTL, nasal type, and surgery for some patients; however, their value for treating PGINKTL remains unknown.…”