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In this retrospective, multi\u2010center study of 755 newly diagnosed ENKTL patients, 17.9% received first\u2010line PD1i. Despite harboring more adverse risk features, the PD1i group showed significantly improved progression\u2010free survival (hazard ratio\u2009=\u20090.62,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007) and overall survival (hazard ratio\u2009=\u20090.55,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.027) after a median follow\u2010up of 32.9\u2009months. The benefit was also observed in key subgroups (non\u2010upper aerodigestive tract, advanced stage, intermediate\/high\u2010risk). Conventional multivariate Cox regression before propensity score matching, robust multivariate Cox analysis after matching, and the time\u2010varying Cox model employed in landmark analysis consistently demonstrated that PD1i therapy served as an independent favorable prognostic factor for both progression\u2010free survival and overall survival. The random forest algorithm revealed enhanced efficacy with PD1i\u2010asparaginase combination therapy, showing about a 50% reduction in event probability, particularly in advanced\u2010stage and intermediate\/high\u2010risk patients. Multi\u2010state survival modeling indicated PD1i primarily delays disease progression rather than post\u2010progression survival. Safety data showed that adding PD1i to asparaginase\u2010based chemotherapy resulted in an expected increase in hematologic toxicities, but with a reduced risk of severe\/fatal infections and rare severe immune\u2010related adverse events, demonstrating a favorable risk\u2013benefit profile. Overall, in this study, frontline PD1i, particularly in combination with asparaginase, yielded significantly improved outcomes and demonstrated a manageable safety profile in intermediate\u2010\/high\u2010risk and advanced ENKTL. This evidence supports its incorporation into first\u2010line treatment and underscores the need for prospective randomized trials.\n                  <\/jats:p>","DOI":"10.1002\/ajh.70341","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T01:55:07Z","timestamp":1777254907000},"page":"1748-1762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Outcomes With First\u2010Line\n                    <scp>PD1<\/scp>\n                    Inhibitors in Extranodal\n                    <scp>NK\/T\u2010Cell<\/scp>\n                    Lymphoma: A Comparative Analysis From a 755\u2010Patient Multicenter Cohort"],"prefix":"10.1002","volume":"101","author":[{"given":"Hailing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hematology Jiangsu Province Hospital, the First Affiliated Hospital With Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hematology Northern Jiangsu People's Hospital Affiliated to Yangzhou University  Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-7230","authenticated-orcid":false,"given":"Chunling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University  Huaian Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiong","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Hematology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Hematology The First Affiliated Hospital of Ningbo University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Hematology The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuzhang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Hematology The Third Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People's Hospital  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9695-4674","authenticated-orcid":false,"given":"Hongming","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hematology The Affiliated Hospital of Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinning","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Hematology The Affiliated Jiangning Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology Jiangsu Province Hospital, the First Affiliated Hospital With Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University  Nanjing Jiangsu 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Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Hematology Jiangsu Province Hospital, the First Affiliated Hospital With Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haorui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Hematology Jiangsu Province Hospital, the First Affiliated Hospital With Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University  Nanjing Jiangsu 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