Cancer Research and Treatment

Original Articles

Hematologic malignancy

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea: Ji Yun Lee, Ji Hyun Kwon, Joon Young Hur, Jun Ho Yi, Ji Hyun Lee, Hyungwoo Cho, Young Rok Do, Jae-Cheol Jo, Hye Jin Kang, Yougil Koh, Won Sik Lee, Sung Nam Lim, Sang Eun Yoon, Seok Jin Kim, Jeong-Ok Lee; Cancer Res Treat. 2024;56(2):681-687. Published online November 10, 2023; DOI: https://doi.org/10.4143/crt.2023.1042

Purpose
Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers.
Materials and Methods
Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022.
Results
The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs.
Conclusion
In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

Citations

Citations to this article as recorded by

Anti-PD-1 antibody combined with P-GEMOX chemotherapy versus P-GEMOX chemotherapy with or without autologous stem-cell transplantation for previously untreated advanced natural killer/T cell lymphoma: a retrospective cohort study
Qihua Zou, Yi Cao, Liang Wang, Wuping Li, Qingsong Yin, Yudan Wu, Hongmei Jing, Zhigang Peng, Xiuhua Sun, Jun Rao, Ying Chen, Hongyu Zhang, Dongfeng Zeng, Bingzong Li, Ying Zhao, Xudong Zhang, Yuchen Zhang, Yan Gao, Bing Bai, Yi Xia, Yu Fang, Zouxiang Che
Blood Cancer Journal.2026;[Epub] CrossRef
Molecular biologic and Epstein-Barr virologic advances in extranodal natural killer/T cell lymphoma over the past four decades
Yasuaki Harabuchi
Auris Nasus Larynx.2026; 53(3): 393. CrossRef
Immunotherapy in NK/T-Cell Lymphoma: Mechanisms, Clinical Evidence, Resistance, and Emerging Multimodal Strategies
Qihao Zhang, Xin Wang
Cancers.2026; 18(9): 1358. CrossRef
Outcomes With First‐Line PD1 Inhibitors in Extranodal NK/T‐Cell Lymphoma: A Comparative Analysis From a 755‐Patient Multicenter Cohort
Hailing Liu, Mei Sun, Chunling Wang, Xiaoqiong Tang, Lixia Sheng, Jie Ma, Xuzhang Lu, Hongming Huang, Jinning Shi, Ran Li, Jing Zhang, Manling Chen, Lei Cao, Haorui Shen, Jianyong Li, Wei Wang, Xia Zhao, Kaiyang Ding, Lei Fan
American Journal of Hematology.2026;[Epub] CrossRef
An evaluation of sugemalimab for the treatment of relapsed or refractory extranodal natural killer T-cell lymphoma
Yingfang Feng, Xia Liu, Jingwei Yu, Zheng Song, Lanfang Li, Lihua Qiu, Shiyong Zhou, Zhengzi Qian, Xianhuo Wang, Huilai Zhang
Expert Opinion on Biological Therapy.2025; 25(1): 9. CrossRef
Early growth response 1 as a key regulator of PD-L1 expression and immune evasion in extranodal NK/T-cell lymphoma
Ji Yun Lee, Kui-Jin Kim, Woochan Park, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Tae Min Kim, Jin Ho Paik
Blood Cancer Journal.2025;[Epub] CrossRef
Efficacy of combined CD38 and PD-1 inhibition with isatuximab and cemiplimab for relapsed/refractory NK/T-cell lymphoma
Seok Jin Kim, Jing Quan Lim, Sang Eun Yoon, Deok-Hwan Yang, Ji Hyun Lee, Sung Yong Oh, Yoon Seok Choi, Seong Hyun Jeong, Min Kyoung Kim, Sung Nam Lim, Junhun Cho, Bon Park, Kyung Ju Ryu, Seunghyun Choi, Yoon Park, Kerry May Huifen Lim, Nur Ayuni Binte Muh
Blood.2025; 146(2): 155. CrossRef
Pembrolizumab

Reactions Weekly.2024; 2025(1): 390. CrossRef

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A New Prognostic Index for Extranodal Natural Killer/T-Cell Lymphoma:Incorporation of Serum β-2 Microglobulin to PINK: Sora Kang, Hyungwoo Cho, Shin Kim, Kyoungmin Lee, Eun Hee Kang, Jung Sun Park, Yoon Sei Lee, Chan-Sik Park, Heounjeong Go, Jooryung Huh, Jin Sook Ryu, Sang-Wook Lee, Seok Jin Kim, Won Seog Kim, Sang Eun Yoon, Young Hyeh Ko, Cheolwon Suh; Cancer Res Treat. 2023;55(1):314-324. Published online March 31, 2022; DOI: https://doi.org/10.4143/crt.2022.015

Abstract PDF Supplementary Material PubReader ePub

Purpose
Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline–based therapy. We aimed to evaluate the prognostic implications of serum β-2 microglobulin (β2M) in the context of PINK and proposed a new prognostic model.
Materials and Methods
A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum β2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum β2M into PINK was proposed and validated in an independent validation cohort (n=88).
Results
The patients’ median age was 53.5 years (range, 19 to 80 years). Patients with high serum β2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum β2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum β-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort.
Conclusion
Serum β2M is an independent prognostic factor for ENKTL patients. The new serum β2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.

Citations

Citations to this article as recorded by

Epstein‐Barr Virus‐positive NK/T‐cell Malignancies in Poland: Distinctive Features, Therapeutic Strategies, and Survival Insights—The Real‐world Retrospective Report of the Polish Lymphoma Research Group
Kateryna Filonenko, Ewa Paszkiewicz‐Kozik, Joanna Drozd‐Sokolowska, Marcin Szymanski, Agnieszka Giza, Anna Kopinska, Ewa Chmielowska, Jan Maciej Zaucha
Asia-Pacific Journal of Clinical Oncology.2026;[Epub] CrossRef
A Bloody Mimic of Crohn’s Disease: Primary Intestinal EBV-Positive NK/T-Cell Lymphoma
Alexander Iacobucci, Joshua Norman, Elsie Ennin, Sebastian Fernandez-Pol, George Triadafilopoulos, Grant Barber
Digestive Diseases and Sciences.2026;[Epub] CrossRef
Beta-2 microglobulin in lymphoma
Gaurav Gupta, Muhammad Afzal, Ahsas Goyal, G. PadmaPriya, Manish Srivastava, Kattela Chennakesavulu, Biswaranjan Mohanty, A. Rekha, Avijit Mazumder, Kavita Goyal, Haider Ali, Moyad Shahwan
Clinica Chimica Acta.2025; 576: 120418. CrossRef
Asparaginase Hypersensitivity Reactions in NK/T-Cell Lymphomas
Javier Varela Gonzalez-Aller, Pablo Nadal, Salome Cañizares, Carmen Muñoz, Anna Valer, Eva Gonzalez-Barca, Eva Domingo, Ana Sureda, Silvana Novelli
Clinics and Practice.2025; 15(11): 211. CrossRef
Elevated serum IL-6 and total IgEAb are associated with poor survival in natural killer/T-cell lymphoma
Yun Hui, Yingjun Gao, Jiawei Li, Qingtao Kong, Yuanyuan Duan, Haibo Liu, Fang Liu, Hong Sang
Annals of Hematology.2024; 103(4): 1285. CrossRef
Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients
Theodoros P. Vassilakopoulos, Maria Arapaki, Panagiotis T. Diamantopoulos, Athanasios Liaskas, Fotios Panitsas, Marina P. Siakantaris, Maria Dimou, Styliani I. Kokoris, Sotirios Sachanas, Marina Belia, Chrysovalantou Chatzidimitriou, Elianna A. Konstantin
Cancers.2024; 16(2): 238. CrossRef
Prognostic Value of18F-FDG PET/CT Radiomics in Extranodal Nasal-Type NK/T Cell Lymphoma
Yu Luo, Zhun Huang, Zihan Gao, Bingbing Wang, Yanwei Zhang, Yan Bai, Qingxia Wu, Meiyun Wang
Korean Journal of Radiology.2024; 25(2): 189. CrossRef
A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase
Ziyuan Shen, Xudong Zhang, Yujie Li, Xicheng Chen, Xing Xing, Hao Zhang, Jingjing Ye, Ling Wang, Tao Jia, Taigang Zhu, Yuqing Miao, Chunling Wang, Hui Liu, Liang Wang, Wei Sang
Future Oncology.2024; 20(28): 2071. CrossRef

11,661 View
141 Download
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