Improved prognosis of advanced‐stage extranodal NK/T‐cell lymphoma: results of the NKEA‐Next study

Abstract

Background: Extranodal NK/T-cell lymphoma (ENKL) is a particular subtype of lymphoma that is characterized by the expression of multi-drug resistance-associated P-glycoprotein. Although the advent of non-anthracycline-based and L-asparaginase containing chemotherapy has contributed to enhancing the prognosis of ENKL patients, recent clinical results of ENKL patients have not been well assessed. Method: A cooperative NKEA-Next study (UMIN 000046300) was performed in Japan to gather data on ENKL patients diagnosed between 2014 and 2021. Data from advanced-stage ENKL patients were examined. Results of limited-stage patients were presented elsewhere (ASCO 2023). Results: A total of 351 patients with ENKL were included in the NKEA-Next study. Among these, 116 patients (33%; 5 with stage III and 111 with stage IV) were in an advanced stage. The median age of the advanced-stage patients was 59.5 years (range: 19–90) and 59% were male. Thirty-five percent of the advanced-stage patients had poor performance status (2–4), and 53% had B symptoms at diagnosis. Of the 111 patients with stage IV disease, 94 (85%) had two or more extranodal involvement, including nasal/paranasal area (65%), bone or bone marrow (44%), skin (44%), lung (18%), liver (17%), spleen (14%) and central nervous system (10%). The most common first-line treatment was SMILE (52%), followed by DeVIC (30%) and CHOP (10%), although 10 patients did not receive any treatments due to poor general condition. The 2-year overall survival (OS) of the advanced-stage patients was 38.2%, which was significantly improved in the recent era (25.2% for the year 2014–2017 vs. 49.8% for the year 2018–2021; P = 0.01). Patients treated with SMILE had significantly longer survival time than those treated with DeVIC or CHOP (2y-OS: 57.1%, 35.8% and 0%, respectively; P < 0.001). The overall response rate was significantly higher in patients treated with SMILE (74%) than those treated with DeVIC (58%) and CHOP (18%). The proportion of patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) was also significantly higher in patients treated with SMILE than the other regimens (65% vs. 18%, P < 0.001). The prognosis was significantly better in patients who underwent HSCT than in those who did not (2-year OS: 66.8% vs. 17.6%, P < 0.001). Multivariate analysis confirmed that patients who underwent HSCT had significantly better OS [hazard ratio (HR) 0.2, 95% confidence interval (CI) 0.1–0.5, P < 0.001] and treatment with SMILE was identified as almost significant factor for better OS (HR 0.6, 95% CI: 0.3–1.0, P = 0.06). Keywords: Aggressive T-cell non-Hodgkin lymphoma, Chemotherapy, Extranodal non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. A. Fujimoto Honoraria: Chugai pharmaceutical co. ltd, Meiji Seika Pharma, Sanofi K. Miyazaki Honoraria: Chugai Pharma, SymBio Pharmaceuticals, Janssen, Eisai, Nippon Shinyaku, AstraZeneca, Bristol-Myers Squibb Japan, Meiji Seika Kaisha, Abbvie, Novartis, Incyte, and Asahi Kasei Research funding: Eisai, Takeda, Nippon Shinyaku, Otsuka, Chugai Pharma, Asahi Kasei, Sumitomo Dainippon Pharma Oncology and Zenyaku Kogyo N. Asano Honoraria: Takeda Pharmaceutical Company Limited K. Yakushijin Honoraria: Pfizer, Kyowa Kirin, Chugai W. Munakata Honoraria: Celgene, Janssen Pharmaceutical, Takeda Pharmaceutical, ONO PHARMACEUTICAL, Eisai Chugai Pharmaceutical, Novartis Pharma, Bristol-Myers Squibb, AstraZeneca, SymBio Pharmaceuticals Genmab, Mundipharma, NIPPON SHINYAKU, Gilead Sciences, Nippon Kayaku Research funding: Janssen Pharmaceutical, ONO PHARMACEUTICAL, Kyowa Kirin, Genmab, NIPPON SHINYAKU M. Hirano Honoraria: Eisai Co., Ltd T. Maeda Honoraria: Bristol Myers Squibb, Chugai, Janssen, Nippon Shinyaku, Novartis, Ono, Sanofi J. Takizawa Honoraria: AstraZeneca, Kyowa-Kirin, Abbvie, Chugai, Jansen, Novartis, Ono Research funding: AstraZeneca, Kyowa-Kirin, Abbvie, Eisai, Chugai, Jansen, Novartis R. Sakai Honoraria: Bristol Myers Squibb, Chugai Pharma, Janssen, Kyowa Kirin, Meiji Seika Pharma, Nippon Shinyaku, Mundipharma, SymBio pharmaceuticals, Takeda Pharmaceutical, CSL Behring K.K, Eisai, AstraZeneca plc, Nihon Medi-Physics, Sanofi S.A., Towa Phamaceutical, Research funding: Chugai Pharma, Kyowa Kirin, TAIHO Phamaceutical N. Fukuhara Honoraria: Chugai pharma, Genmab, Abbvie, Takeda, Eli Lilly, astrazeneca, Meiji Seika, Ono Pharmacuetical, Janssen, Bristol-Myers Squibb, Eisai, Kyowa-Hakko Kirin, Symbio and Novartis Research funding: Chugai pharma, Genmab, Abbvie, Takeda, Eli Lilly, Incyte and Chordia Therapeu M. Yamaguchi Honoraria: AbbVie, Bristol Myers Squibb, Chugai Pharma, Janssen, Kyowa Kirin, Meiji Seika Pharma, MSD, Nippon Shinyaku, SymBio pharmaceuticals, Takeda Pharmaceutical Research funding: Chugai pharma, Genmab, Abbvie, Takeda and Eli Lilly R. Suzuki Honoraria: Kyowa-kirin Chugai Bristol-Meyer Squib Eisai MSD Shionogi Janssen Abbvie Takeda Meiji Seika Ohtsuka Sumitomo Dainippon Novartis AstraZeneca Nippon Shinyaku Research funding: Kyowa-kirin Chugai Taiho Ohtsuka Takeda Shionogi Eisai Meiji Seika Sysmex