Cancer Research and Treatment

Original Articles

Hematologic malignancy

Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study: Yu Ri Kim, Jin Seok Kim, Won Seog Kim, Hyeon Seok Eom, Deok-Hwan Yang, Sung Hwa Bae, Hyo Jung Kim, Jae Hoon Lee, Suk-Joong Oh, Sung-Soo Yoon, Jae-Yong Kwak, Chul Won Choi, Min Kyoung Kim, Sung Young Oh, Hye Jin Kang, Seung Hyun Nam, Hyeok Shim, Joon Seong Park, Yeung-Chul Mun, Cheolwon Suh, the Korean Society of Hematology Lymphoma Working Party; Cancer Res Treat. 2023;55(4):1355-1362. Published online March 30, 2023; DOI: https://doi.org/10.4143/crt.2023.271

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Purpose
This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL).
Materials and Methods
Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy.
Results
Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016).
Conclusion
Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

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Design, Conduct, and Analysis of Externally Controlled Trials
Jiali Liu, Minghong Yao, Mingqi Wang, Wan Jie, Yanmei Liu, Xiaochao Luo, Jiayidaer Huan, Kelin Deng, Ke Deng, Kang Zou, Ying Zhang, Ling Li, Xin Sun
JAMA Network Open.2025; 8(9): e2530277. CrossRef

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Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial: Xueying Li, He Huang, Bing Xu, Hongqiang Guo, Yingcheng Lin, Sheng Ye, Jiqun Yi, Wenyu Li, Xiangyuan Wu, Wei Wang, Hongyu Zhan, Derong Xie, Jiewen Peng, Yabing Cao, Xingxiang Pu, Chengcheng Guo, Huangming Hong, Zhao Wang, Xiaojie Fang, Yong Zhou, Suxia Lin, Qing Liu, Tongyu Lin; Cancer Res Treat. 2019;51(3):919-932. Published online October 2, 2018; DOI: https://doi.org/10.4143/crt.2018.230

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Purpose
Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population.
Materials and Methods
Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP- 14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities.
Results
Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21.
Conclusion
R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

Citations

Citations to this article as recorded by

Definitions and use of tumor bulk in phase 3 lymphoma trials: a comprehensive literature review
Luke Wang, Eliza Chung, Cameron Wellard, Allison Barraclough, Belinda A. Campbell, Geoffrey Chong, Pietro R. Di Ciaccio, Gareth P. Gregory, Greg Hapgood, Anna M. Johnston, Constantine Tam, Stephen Opat, Erica M. Wood, Zoe K. McQuilten, Eliza A. Hawkes
Blood Advances.2025; 9(9): 2275. CrossRef
Prediction of 5‐year overall survival of diffuse large B‐cell lymphoma on the pola‐R‐CHP regimen based on 2‐year event‐free survival and progression‐free survival
Wan‐Ru Zhang, Xin Liu, Qiu‐Zi Zhong, Tao Wu, Yong Yang, Bo Chen, Hao Jing, Yuan Tang, Jing Jin, Yue‐Ping Liu, Yong‐Wen Song, Hui Fang, Ning‐Ning Lu, Ning Li, Yi‐Rui Zhai, Wen‐Wen Zhang, Shu‐Lian Wang, Fan Chen, Lin Yin, Shu‐Nan Qi, Ye‐Xiong Li
Cancer Medicine.2024;[Epub] CrossRef
Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study
Yan Qin, Yongping Song, Dong Wang, Ou Bai, Jifeng Feng, Xiuhua Sun, Lihua Qiu, Jianmin Yang, Yu Yang, Zhao Wang, Jianda Hu, Huaqing Wang, Hang Su, Zhengming Jin, Wenbin Qian, Chuan Jin, Mingzhi Zhang, Ding Yu, Li Liu, Guoan Chen, Yarong Li, Tao Sun, Jie J
BMC Cancer.2024;[Epub] CrossRef
Palmitic acid reduces the methylation of the FOXO1 promoter to suppress the development of diffuse large B-cell lymphoma via modulating the miR-429/DNMT3A axis
Weiming LI, Ming GAO, Weili XUE, Xiaoli LI, Yu CHANG, Kaixin ZHANG, Chenyu WEN, Mingzhi ZHANG
Chinese Journal of Natural Medicines.2024; 22(6): 554. CrossRef
Prophylaxis for Pneumocystis carinii pneumonia in non-Hodgkin’s lymphoma undergoing R-CHOP21 in China: a meta-analysis and cost-effectiveness analysis
Xiaojia Huang, Xiaoting Huang, Shen Lin, Shaohong Luo, Liangliang Dong, Dong Lin, Yaping Huang, Chen Xie, Dongni Nian, Xiongwei Xu, Xiuhua Weng
BMJ Open.2023; 13(3): e068943. CrossRef
Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving S
Yu Ri Kim, Jin Seok Kim, Won Seog Kim, Hyeon Seok Eom, Deok-Hwan Yang, Sung Hwa Bae, Hyo Jung Kim, Jae Hoon Lee, Suk-Joong Oh, Sung-Soo Yoon, Jae-Yong Kwak, Chul Won Choi, Min Kyoung Kim, Sung Young Oh, Hye Jin Kang, Seung Hyun Nam, Hyeok Shim, Joon Seong
Cancer Research and Treatment.2023; 55(4): 1355. CrossRef
Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study
Lorenz Thurner, Marita Ziepert, Christian Berdel, Christian Schmidt, Peter Borchmann, Dominic Kaddu-Mulindwa, Andreas Viardot, Mathias Witzens-Harig, Judith Dierlamm, Mathias Haenel, Bernd Metzner, Gerald Wulf, Eva Lengfelder, Ulrich B. Keller, Norbert Fr
HemaSphere.2023; 7(7): e904. CrossRef
Treatment of Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis
Aleksander Sergeevich Luchinin
Clinical Oncohematology.2022; 15(2): 130. CrossRef
The prognostic roles of hepatitis B virus antibody in diffuse large B-cell lymphoma patients
Shunfeng Hu, Na Chen, Kang Lu, Changqing Zhen, Xiaohui Sui, Xiaosheng Fang, Ying Li, Yingshu Luo, Xiangxiang Zhou, Xin Wang
Leukemia & Lymphoma.2021; 62(6): 1335. CrossRef
Primary diffuse large B-cell lymphoma of the fallopian tube treated with a combination of surgery and chemotherapy
Ye Zhou, Chao Zhang, Yingying Gong, Linqing Yang, Yunfei Wang
Medicine.2021; 100(3): e24049. CrossRef
Impact and Intricacies of Bone Marrow Microenvironment in B-cell Lymphomas: From Biology to Therapy
Anuvrat Sircar, Sayan Chowdhury, Amber Hart, William Bell, Satishkumar Singh, Lalit Sehgal, Narendranath Epperla
International Journal of Molecular Sciences.2020; 21(3): 904. CrossRef
Association of progression-free or event-free survival with overall survival in diffuse large B-cell lymphoma after immunochemotherapy: a systematic review
Jie Zhu, Yong Yang, Jin Tao, Shu-Lian Wang, Bo Chen, Jian-Rong Dai, Chen Hu, Shu-Nan Qi, Ye-Xiong Li
Leukemia.2020; 34(10): 2576. CrossRef
Front-Line Treatment of High Grade B Cell Non-Hodgkin Lymphoma
Murali Kesavan, Toby A. Eyre, Graham P. Collins
Current Hematologic Malignancy Reports.2019; 14(4): 207. CrossRef
Immunohistochemical Subtype and Parameters of International Prognostic Index in the New Prognostic Model of Diffuse Large B-Cell Lymphoma
S. V. Samarina, A. S. Luchinin, N. V. Minaeva, I. V. Paramonov, D. A. D’yakonov, E. V. Vaneeva, V. A. Rosin, S. V. Gritsaev
Clinical Oncohematology.2019; 12(4): 385. CrossRef

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Case Report

Human Herpesvirus 8–Unrelated Primary Effusion Lymphoma–Like Lymphoma in an Elderly Korean Patient with a Good Response to Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone: Junghoon Shin, Jeong-Ok Lee, Ji-Young Choe, Soo-Mee Bang, Jong-Seok Lee; Cancer Res Treat. 2017;49(1):274-278. Published online June 10, 2016; DOI: https://doi.org/10.4143/crt.2016.076

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Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin’s lymphoma arising from a B-cell lineage characterized by the formation of malignant effusion in body cavities without evidence of a detectable tumor. The effusion contains tumor cells universally infected with human herpesvirus 8 (HHV8), which is the critical factor differentiating PEL from HHV8-unrelated PEL-like lymphoma (PEL-LL). This report describes a 77-year-old male patient with pleural effusion and ascites, containing lymphoma cells expressing a B-cell phenotype, but without markers of HHV8 in immunocytochemical analysis. The patient was diagnosed with PEL-LL and treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), which resulted in a complete remission. The patient is currently disease-free 15 months post-treatment. To the best of our knowledge, this is the first report on administration of R-CHOP in a PEL-LL patient in South Korea.

Citations

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HIV-positive and HHV-8-negative primary effusion lymphoma complicated with coronary heart disease: a Case Report and literature review
Wei Zhang, Ying Zhang, Jing Yuan
Frontiers in Medicine.2025;[Epub] CrossRef
Fluid overload-associated large B-cell lymphoma: two case report and review of literature
Liudi Chang, Zhaobo Yang, Cuicui Yang, Yuxiao Wang, Dan Li, Hui Wang, Lanlan Zang, Yuanyuan Zhang
Frontiers in Oncology.2025;[Epub] CrossRef
Primary Effusion Lymphoma-like Lymphoma Mimicking Tuberculous Pleural Effusion: Three Case Reports and a Literature Review
Kenta Hayashino, Yusuke Meguri, Ryouya Yukawa, Aya Komura, Makoto Nakamura, Chikamasa Yoshida, Kazuhiko Yamamoto, Wakako Oda, Kenji Imajo
Internal Medicine.2023; 62(17): 2531. CrossRef
A rare case of fluid overload-associated large B-cell lymphoma and antigen loss at relapse
Xue Yan, Bin Chen, Hongxia Jing, Zhinan Yang, Ting Zhang, Yani Lin, Jinning Shi
Journal of Hematopathology.2023; 16(4): 235. CrossRef
Primary Effusion Lymphoma: A Timely Review on the Association with HIV, HHV8, and EBV
Chih-Yi Liu, Bo-Jung Chen, Shih-Sung Chuang
Diagnostics.2022; 12(3): 713. CrossRef
Targeting VEGF with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8‐unrelated effusion large B‐cell lymphoma in vivo
Fumiya Ogasawara, Tomonori Higuchi, Tomohiro Nishimori, Yumiko Hashida, Kensuke Kojima, Masanori Daibata
Journal of Cellular and Molecular Medicine.2022; 26(22): 5580. CrossRef
Diagnostic significance of adenosine deaminase in pleural effusate for primary effusion lymphoma–like lymphoma
Soichiro Nakako, Mitsushige Nishimura, Yoshiro Murakami, Atsuko Mugitani
Clinical Case Reports.2020; 8(12): 3215. CrossRef
Body Cavity–Based Lymphoma in a Country with Low Human Immunodeficiency Virus Prevalence: A Series of 17 Cases from the Consortium for Improving Survival of Lymphoma
Junghoon Shin, Young Hyeh Ko, Sung Yong Oh, Dok Hyun Yoon, Jeong-Ok Lee, Jin Seok Kim, Yong Park, Ho Jin Shin, Seok Jin Kim, Jong Ho Won, Sung-Soo Yoon, Won Seog Kim, Youngil Koh
Cancer Research and Treatment.2019; 51(4): 1302. CrossRef
Age and CD20 Expression Are Significant Prognostic Factors in Human Herpes Virus-8-negative Effusion-based Lymphoma
Tomomi Kubota, Yosuke Sasaki, Eisuke Shiozawa, Masafumi Takimoto, Tsunekazu Hishima, Ja-Mun Chong
American Journal of Surgical Pathology.2018; 42(12): 1607. CrossRef
A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma
Daisuke Usuda, Masahisa Arahata, Kento Takeshima, Ryusho Sangen, Akiteru Takamura, Yasuhiro Kawai, Yuji Kasamaki, Yoshitsugu Iinuma, Tsugiyasu Kanda
Case Reports in Oncology.2017; 10(3): 1013. CrossRef

10,575 View
200 Download
10 Web of Science
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