Treatment and Prognosis of Newly Diagnosed Advanced-Stage Extranodal Natural Killer/T-Cell Lymphoma: A Single-Center Real-World Study across Two Decades

Abstract

<b><i>Introduction:</i></b> Although there is now a consensus on asparaginase-based chemotherapy regimens in the treatment of advanced-stage extranodal natural killer/T-cell lymphomas (ENKTCLs), patient survival in the real-world setting is still not optimistic according to previous literature reports, and the optimal chemotherapeutic regimens and integration of different therapeutic methods under the concept of combined-modality treatment still need to be further explored and verified. <b><i>Methods:</i></b> Newly diagnosed stage Ⅲ/Ⅳ ENKTCL patients from Chinese National Cancer Center in the last two decades were retrospectively collected and analyzed. Overall survival (OS) and progression-free survival (PFS) were determined as primary endpoints. Log-rank tests and Cox proportional hazard models were performed to test for survival differences between subgroups and examine the univariable and multivariable associations. <b><i>Results:</i></b> The study included 83 newly diagnosed stage Ⅲ/Ⅳ ENKTCL patients and reported a median OS of 26.07 months and an estimated 5-year OS of 41.3% with a median follow-up of 82.13 months. First-line asparaginase-based regimens compared to non-asparaginase-based regimens significantly prolonged PFS (<i>p</i> = 0.007; HR = 0.48, <i>p</i> = 0.020) and showed a tendency to improve OS (<i>p</i> = 0.064; HR = 0.74, <i>p</i> = 0.359). Gemcitabine-based regimens also exhibited a trend toward improved PFS (<i>p</i> = 0.048; HR = 0.59, <i>p</i> = 0.164) and OS (<i>p</i> = 0.008; HR = 0.67, <i>p</i> = 0.282) compared to non-gemcitabine-based ones. The asparaginase and gemcitabine combinations yielded a 5-year OS of 55.0% and led to significantly superior PFS (<i>p</i> = 0.020; HR = 0.40, <i>p</i> = 0.022) and slightly better OS (<i>p</i> = 0.054; HR = 0.79, <i>p</i> = 0.495) compared to the remaining regimens. First-line combined-modality treatment integrating chemotherapy and radiotherapy improved PFS (<i>p</i> = 0.051) and OS (<i>p</i> = 0.036) compared to chemotherapy alone. Four autologous hematopoietic stem cell transplantation recipients reached a median OS of 58.34 months. <b><i>Conclusion:</i></b> Asparaginase and gemcitabine alone brought a favorable impact on PFS and OS; and the asparaginase and gemcitabine combination chemotherapy yielded the optimal efficacy, response duration, and survival outcomes. Combined-modality treatment including potent chemotherapy supplemented by radiotherapy and/or consolidative transplantation could improve prognosis in newly diagnosed advanced-stage ENKTCLs.