Multicenter real-world study of newly diagnosed advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL): Proposal for intensive therapy.

Abstract

e19523 Background: Advanced-stage ENKTL is characterized by its low prevalence, poor prognosis, and inconclusive optimal therapy. The present study investigated the treatment of newly diagnosed advanced-stage ENKTLs. Methods: Newly diagnosed stage III/IV ENKTL patients from two large-scale Chinese cancer centers in the last 10-15 years were retrospectively collected and analyzed. Results: With a median follow-up of 75.03 (range, 0.33-292.13) months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 (range, 0.33-292.13) months, and estimated 1-, 2-, 3-, and 5-year OS were 59.5%, 46.3%, 41.8%, and 35.1%, respectively. First-line multi-modality therapy(n=89) significantly prolonged OS compared to single-modality therapy(n=106)( P<0.001). Chemotherapy(CT)+radiotherapy(RT)(n=47) compared to CT alone(n=93)( P=0.007), and hematopoietic stem cell transplantation(HSCT)(n=20) compared to non-HSCT(n=175)( P<0.001) both significantly improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission(n=28) led to comparable OS( P=0.160), with no significant difference in baseline characteristics( P>0.05). Four long-term survival patients treated with chidamide maintenance therapy(MT) achieved a median progression-free survival(PFS) of 55.83(range, 53.27-92.33) months and a mOS of 60.65(range, 53.70-95.70) months, preliminarily indicating its positive impact on prognosis. Regarding CT, anthracycline(ANT)-based regimens(n=60), compared to non-ANT-based ones(n=119), led to significantly inferior PFS( P=0.031) and OS( P=0.010); while asparaginase(ASP)-(n=123) compared to non-ASP-(n=56), and gemcitabine(GEM)-(n=56) compared to non-GEM-based(n=123) regimens, both prolonged PFS( P=0.005; P=0.009) and OS( P=0.086; P=0.003). Multivariate analysis further showed that GEM-based regimens improved PFS(HR=0.691, P=0.061) and OS(HR=0.624, P=0.037) compared to non-GEM-based ones. The GEM+ASP(n=42) combinations slightly improved PFS and OS compared to regimens containing either GEM(n=14) or ASP(n=56) alone( P>0.05). The GEM+ASP combinations led to significantly superior PFS( P=0.058[log-rank test], P=0.036[Breslow test]) and OS( P=0.008) compared to the ANT+ASP combinations. First-line “intensive therapy”, including CT(particularly GEM+ASP regimens), RT, HSCT, and chidamide MT, was therefore proposed, and could improve long-term survival for advanced-stage ENKTLs. Conclusions: We propose the first-line “intensive therapy” for newly diagnosed advanced-stage ENKTLs, including CT, RT, HSCT, and chidamide MT. The GEM+ASP combinations appear to yield the optimal efficacy and survival. RT, consolidative HSCT, or chidamide MT are recommended.