Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study

Jian-Qiu Wu, Yong-Ping Song, Li-Ping Su, Ming-Zhi Zhang, Wei Li, Yu Hu, Xiao-Hong Zhang, Yu-Huan Gao, Zuo-Xing Niu, Ru Feng, Wei Wang, Jie-Wen Peng, Xiao-Lin Li, Xue-Nong Ouyang, Chang-Ping Wu, Wei-Jing Zhang, Yun Zeng, Zhen Xiao, Ying-Min Liang, Yong-Zhi Zhuang, Ji-Shi Wang, Zi-Min Sun, Hai Bai, Tong-Jian Cui, Ji-Feng Feng, Jian-Qiu Wu, Yong-Ping Song, Li-Ping Su, Ming-Zhi Zhang, Wei Li, Yu Hu, Xiao-Hong Zhang, Yu-Huan Gao, Zuo-Xing Niu, Ru Feng, Wei Wang, Jie-Wen Peng, Xiao-Lin Li, Xue-Nong Ouyang, Chang-Ping Wu, Wei-Jing Zhang, Yun Zeng, Zhen Xiao, Ying-Min Liang, Yong-Zhi Zhuang, Ji-Shi Wang, Zi-Min Sun, Hai Bai, Tong-Jian Cui, Ji-Feng Feng

Abstract

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.

Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.

Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.

Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.

Trial registration: ClinicalTrials.gov, NCT01340443; https://ichgcp.net/clinical-trials-registry/NCT01340443.

Keywords: Asian; Hematopoietic Malignancy; Hepatitis B Virus; Observational Study; Rituximab.

Conflict of interest statement

There are no conflicts of interest

Figures

Figure 1
Figure 1
Univariate and multivariate analyses using Cox regression for progression-free survival. (a) Univariate analysis. (b) Multivariate analysis. ECOG: Eastern Cooperative Oncology Group performance status; HR: Hazard ratio; CI: Confidence interval; HBsAg: Hepatitis B surface antigen; HBcAb: Hepatitis B core antibody.
Figure 2
Figure 2
Univariate and multivariate analyses using Cox regression for overall survival. (a) Univariate analysis. (b) Multivariate analysis. ECOG: Eastern Cooperative Oncology Group performance status; HR: Hazard ratio; CI: Confidence interval; HBsAg: Hepatitis B surface antigen; HBcAb: Hepatitis B core antibody.

References

    1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96. doi: 10.3322/CA.2007.0010.
    1. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503–11. doi: 10.1038/35000501.
    1. Zhang YN, Zhou XG, Zhang SH, Wang P, Zhang CH, Huang SF, et al. Clinicopathologic study of 369 B-cell non-Hodgkin lymphoma cases, with reference to the 2001 World Health Organization classification of lymphoid neoplasms (in Chinese) Chin J Pathol. 2005;34:193–7. doi: 10.1182/blood-2011-01-293050.
    1. Chinese Society of Hematology, CMA, Committee of Malignant Lymphoma, Chinese Anti.cancer Association, Chinese Society of Hepatology, CMA. Consensus on the management of lymphoma with HBV infection (in Chinese) Chin J Hematol. 2013;34:988–93. doi: 10.3760/cma.j.issn.0253-2727.2013.11.019.
    1. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42. doi: 10.1056/NEJMoa011795.
    1. Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: A randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379–91. doi: 10.1016/S1470-2045(06)70664-7.
    1. Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011;12:1013–22. doi: 10.1016/S1470-2045(11)70235-2.
    1. Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: A randomised controlled trial (RICOVER-60) Lancet Oncol. 2008;9:105–16. doi: 10.1016/S1470-2045(08)70002-0.
    1. Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: A study by the Groupe D'etudes des Lymphomes de L'adulte. Blood. 2010;116:2040–5. doi: 10.1182/blood-2010-03-276246.
    1. Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005;105:1417–23. doi: 10.1182/blood-2004-08-3175.
    1. Lee RS, Bell CM, Singh JM, Hicks LK. Hepatitis B screening before chemotherapy: A survey of practitioners' knowledge, beliefs, and screening practices. J Oncol Pract. 2012;8:325–8. doi: 10.1200/JOP.2012.000597.
    1. Turker K, Oksuzoglu B, Balci E, Uyeturk U, Hascuhadar M. Awareness of hepatitis B virus reactivation among physicians authorized to prescribe chemotherapy. Eur J Intern Med. 2013;24:e90–2. doi: 10.1016/j.ejim.2013.07.008.
    1. Wu J, Song Y, Su L, Xu L, Chen T, Zhao Z, et al. Rituximab plus chemotherapy as first-line treatment in Chinese patients with diffuse large B-cell lymphoma in routine practice: A prospective, multicentre, non-interventional study. BMC Cancer. 2016;16:537. doi: 10.1186/s12885-016-2523-7.
    1. NCI Common Terminology Criteria for Adverse Events (CTCAE) [Last accessed on 2017 Aug 15]. Avaialble from: .
    1. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17:1244. doi: 10.1200/JCO.1999.17.4.
    1. Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: A multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011;12:460–8. doi: 10.1016/S1470-2045(11)70069-9.
    1. Seki R, Ohshima K, Nagafuji K, Fujisaki T, Uike N, Kawano F, et al. Rituximab in combination with CHOP chemotherapy for the treatment of diffuse large B cell lymphoma in Japan: A retrospective analysis of 1,057 cases from Kyushu Lymphoma Study Group. Int J Hematol. 2010;91:258–66. doi: 10.1007/s12185-009-0475-2.
    1. Yang Y, Wang L, Ma Y, Han T, Huang M. The enhanced international prognostic index for diffuse large B-cell lymphoma. Am J Med Sci. 2017;353:459–65. doi: 10.1016/j.amjms.2017.02.002.
    1. Zhong HJ, Xu PP, Zhao WL. Efficacy of additional two cycles of rituximab administration for patients with diffuse large B-cell lymphoma in first remission (in Chinese) Chin J Hematol. 2016;37:756–61. doi: 10.3760/cma.j.issn.0253-2727.2016.09.006.
    1. Riedell P, Carson KR. A drug safety evaluation of rituximab and risk of hepatitis B. Expert Opin Drug Saf. 2014;13:977–87. doi: 10.1517/14740338.2014.918948.
    1. Li H, Zhang HM, Chen LF, Chen YQ, Chen L, Ren H, et al. Prophylactic lamivudine to improve the outcome of HBsAg-positive lymphoma patients during chemotherapy: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2015;39:80–92. doi: 10.1016/j.clinre.2014.07.010.
    1. Tang Z, Li X, Wu S, Liu Y, Qiao Y, Xu D, et al. Risk of hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients with undetectable serum HBV DNA after treatment with rituximab for lymphoma: A meta-analysis. Hepatol Int. 2017;11:429–33. doi: 10.1007/s12072-017-9817-y.
    1. European Association for the Study of the Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85. doi: 10.1016/j.jhep.2012.02.010.
    1. Zelenetz AD, Wierda WG, Abramson JS, Advani RH, Andreadis CB, Bartlett N, et al. Non-Hodgkin's lymphomas, version 1.2013. J Natl Compr Canc Netw. 2013;11:257–72. doi: 10.6004/jnccn.2013.0037.
    1. Burton C, Kaczmarski R, Jan-Mohamed R. Interstitial pneumonitis related to rituximab therapy. N Engl J Med. 2003;348:2690–1. doi: 10.1056/NEJM200306263482619.
    1. Knight C, Maciver F. The cost-effectiveness of rituximab in non-Hodgkin's lymphoma. Expert Rev Pharmacoecon Outcomes Res. 2007;7:319–26. doi: 10.1586/14737167.7.4.319.
    1. Xu XC, Bi C, Chen W. Cost-effectiveness of rituximab in the treatment of diffuse large b-cell non-Hodgkin's lymphoma patients (Dlbcl) in China. Value Health. 2016;19:A888. doi: 10.1016/j.jval.2016.08.271.

Source: PubMed

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