Skip to main content
Top
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Superior efficacy of rituximab-based chemoimmunotherapy as an initial therapy in newly diagnosed patients with B cell indolent lymphomas: long-term results from a single center in China

Authors: Zengjun Li, Fei Li, Shuhua Yi, Zhimin Gu, Zhen Yu, Yan Xu, Xiaoyan Feng, Wei Liu, Dehui Zou, Junyuan Qi, Fenghuang Zhan, Lugui Qiu

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

Rituximab has been confirmed to improve the survival of patients with B cell indolent non-Hodgkin lymphomas (B-iNHLs) in Western world as previously reported, however, it is rarely reported in Chinese cohort. This study is to investigate the efficacy and safety of rituximab-based chemoimmunotherapy and select subpopulations most sensitive to the regimen in Chinese B-iNHL patients.

Methods

334 B-iNHL patients from our center were retrospectively assessed.

Results

Patients received R-based chemoimmunotherapy showed significantly higher rates of overall response (OR) (93.0 % vs. 53.4 %, P < 0.001) and complete response (CR) (63.3 % vs. 16.0 %, P < 0.001) compared with the patients received other therapies. Survival analysis showed that rituximab-based chemoimmunotherapy could obviously improve the progression-free survival (PFS) (110 vs. 49 months, P = 0.001) and overall survival (OS) (120 vs. 72 months, P < 0.001) in patients with B-iNHLs. Interestingly, in chronic lymphocytic leukemia (CLL) patients, we found that the patients with β2-microglobulin (β2-MG) < 3.5 mg/L, lactate dehydrogenase (LDH) < 220 U/L, zeta-chain-associated protein kinase 70 (ZAP-70) negative, and non high-risk genetic abnormality could achieve more benefits from R-based regimens with higher CR rate (P = 0.003, 0.029, 0.013 and 0.038, respectively). Meanwhile, more CLL patients achieved minimal residual disease (MRD) negative after rituximab-based treatment (46.5 % vs. 10.3 %, P < 0.001). Moreover, CLL patients with MRD < 1 %, LDH < 220 U/L, complete remission (CR) or partial remission (PR), β2-MG < 3.5 mg/L and non high-risk cytogenetic abnormality showed superior outcome compared to the controls (P = 0.001, 0.000, 0.000, 0.001 and 0.013, respectively). No other side-effects increased in chemoimmunotherapy group except the elevation of grade 3–4 neutropenia.

Conclusions

Our results demonstrate the superior efficacy of rituximab–based chemoimmunotherapy as an initial therapy in Chinese cohort with newly diagnosed B-iNHLs and further identify subpopulations that are more sensitive to R-based chemoimmunotherapy in CLL group.
Literature
1.
go back to reference Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guide-lines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446–56.CrossRefPubMedPubMedCentral Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guide-lines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446–56.CrossRefPubMedPubMedCentral
2.
go back to reference Dreger P, Döhner H, Ritgen M, Böttcher S, Busch R, Dietrich S, et al. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010;116:2438–47.CrossRefPubMed Dreger P, Döhner H, Ritgen M, Böttcher S, Busch R, Dietrich S, et al. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010;116:2438–47.CrossRefPubMed
3.
go back to reference Hallek M, Pflug N. State of the art treatment of chronic lymphocytic leukaemia. Blood Rev. 2011;25:1–9.CrossRefPubMed Hallek M, Pflug N. State of the art treatment of chronic lymphocytic leukaemia. Blood Rev. 2011;25:1–9.CrossRefPubMed
4.
go back to reference Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 trial): a randomised controlled trial. Lancet. 2007;370:230–9.CrossRefPubMed Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 trial): a randomised controlled trial. Lancet. 2007;370:230–9.CrossRefPubMed
5.
go back to reference Else M, Marín-Niebla A, de la Cruz F, Batty P, Ríos E, Dearden CE, et al. Rituximab, used alone or in combination, is superior to other treatment modalities in splenic marginal zone lymphoma. Br J Haematol. 2012;159:322–8.CrossRefPubMed Else M, Marín-Niebla A, de la Cruz F, Batty P, Ríos E, Dearden CE, et al. Rituximab, used alone or in combination, is superior to other treatment modalities in splenic marginal zone lymphoma. Br J Haematol. 2012;159:322–8.CrossRefPubMed
6.
go back to reference Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: Results of the GELA-GOELAMS FL 2000 study. Blood. 2008;112:4824–31.CrossRefPubMed Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: Results of the GELA-GOELAMS FL 2000 study. Blood. 2008;112:4824–31.CrossRefPubMed
7.
go back to reference Treon SP, Branagan AR, Ioakimidis L, Soumerai JD, Patterson CJ, Turnbull B, et al. Long term outcomes to fludarabine and rituximab in Waldenström macroglobulinemia. Blood. 2009;113:3673–78.CrossRefPubMedPubMedCentral Treon SP, Branagan AR, Ioakimidis L, Soumerai JD, Patterson CJ, Turnbull B, et al. Long term outcomes to fludarabine and rituximab in Waldenström macroglobulinemia. Blood. 2009;113:3673–78.CrossRefPubMedPubMedCentral
8.
go back to reference Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376:1164–74.CrossRefPubMed Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376:1164–74.CrossRefPubMed
9.
go back to reference Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, et al. Phase III Study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008;26:4579–86.CrossRefPubMed Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, et al. Phase III Study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008;26:4579–86.CrossRefPubMed
10.
go back to reference Smith MR. Rituximab (monoclonal anti-CD20 antibody) mechanisms of action and resistance. Oncogene. 2003;22:7359–68.CrossRefPubMed Smith MR. Rituximab (monoclonal anti-CD20 antibody) mechanisms of action and resistance. Oncogene. 2003;22:7359–68.CrossRefPubMed
11.
go back to reference Foon KA, Hallek MJ. Changing paradigms in the treatment of chronic lymphocytic leukemia. Leukemia. 2010;24:500–11.CrossRefPubMed Foon KA, Hallek MJ. Changing paradigms in the treatment of chronic lymphocytic leukemia. Leukemia. 2010;24:500–11.CrossRefPubMed
12.
14.
go back to reference Matutes E, Oscier D, Montalban C, Berger F, Callet-Bauchu E, Dogan A, et al. Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Leukemia. 2008;22:487–95.CrossRefPubMed Matutes E, Oscier D, Montalban C, Berger F, Callet-Bauchu E, Dogan A, et al. Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Leukemia. 2008;22:487–95.CrossRefPubMed
15.
go back to reference Gertz MA. Waldenström macroglobulinemia 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012;87:503–10.CrossRefPubMed Gertz MA. Waldenström macroglobulinemia 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2012;87:503–10.CrossRefPubMed
16.
go back to reference McNamara C, Davies J, Dyer M, Hoskin P, Illidge T, Lyttelton M, et al. Guidelines on the investigation and management of follicular lymphoma. Br J Haematol. 2012;156:446–67.CrossRefPubMed McNamara C, Davies J, Dyer M, Hoskin P, Illidge T, Lyttelton M, et al. Guidelines on the investigation and management of follicular lymphoma. Br J Haematol. 2012;156:446–67.CrossRefPubMed
17.
go back to reference Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, et al. Frontline therapy with rituximab added to the combination of cylophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106:3725–32.CrossRefPubMed Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, et al. Frontline therapy with rituximab added to the combination of cylophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106:3725–32.CrossRefPubMed
18.
go back to reference Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology study. J Clin Oncol. 2007;25:1986–92.CrossRefPubMed Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology study. J Clin Oncol. 2007;25:1986–92.CrossRefPubMed
19.
go back to reference Wu T, Li ZJ, Qiu LG. Complications of chronic lymphocytic leukemia: analysis of 203 cases in China. Leuk Res. 2010;34:e64–5.CrossRefPubMed Wu T, Li ZJ, Qiu LG. Complications of chronic lymphocytic leukemia: analysis of 203 cases in China. Leuk Res. 2010;34:e64–5.CrossRefPubMed
20.
go back to reference Li ZJ, Qiu LG, Wu T, Wang YF, Zou DH, Zhao YZ, et al. The clinical and laboratory features of 263 cases of chronic lymphocytic leukemia. Zhonghua Xue Ye Xue Za Zhi. 2008;29(5):300–3.PubMed Li ZJ, Qiu LG, Wu T, Wang YF, Zou DH, Zhao YZ, et al. The clinical and laboratory features of 263 cases of chronic lymphocytic leukemia. Zhonghua Xue Ye Xue Za Zhi. 2008;29(5):300–3.PubMed
21.
go back to reference Chen L, Zhang Y, Zheng W, Wu Y, Qiao C, Fan L, et al. Distinctive IgVH gene segments usage and mutation status in Chinese patients with chronic lymphocytic leukemia. Leuk Res. 2008;32:1491–8.CrossRefPubMed Chen L, Zhang Y, Zheng W, Wu Y, Qiao C, Fan L, et al. Distinctive IgVH gene segments usage and mutation status in Chinese patients with chronic lymphocytic leukemia. Leuk Res. 2008;32:1491–8.CrossRefPubMed
22.
go back to reference Tam CS, O'Brien S, Wierda W, Kantarjian H, Wen S, Do KA, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112:975–80.CrossRefPubMedPubMedCentral Tam CS, O'Brien S, Wierda W, Kantarjian H, Wen S, Do KA, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112:975–80.CrossRefPubMedPubMedCentral
23.
go back to reference Flinn IW, Neuberg DS, Grever MR, Dewald GW, Bennett JM, Paietta EM, et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007;25:793–8.CrossRefPubMed Flinn IW, Neuberg DS, Grever MR, Dewald GW, Bennett JM, Paietta EM, et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007;25:793–8.CrossRefPubMed
24.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
25.
go back to reference Dimopoulos MA, Gertz MA, Kastritis E, Garcia-Sanz R, Kimby EK, Leblond V, et al. Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia. J Clin Oncol. 2009;27:120–6.CrossRefPubMed Dimopoulos MA, Gertz MA, Kastritis E, Garcia-Sanz R, Kimby EK, Leblond V, et al. Update on treatment recommendations from the Fourth International Workshop on Waldenstrom's Macroglobulinemia. J Clin Oncol. 2009;27:120–6.CrossRefPubMed
26.
go back to reference Ghobrial IM, Fonseca R, Greipp PR, Blood E, Rue M, Vesole DH, et al. Initial immunoglobulin M ‘flare’ after rituximab therapy in patients diagnosed with Waldenström macroglobulinemia: an Eastern Cooperative Oncology Group Study. Cancer. 2004;101:2593–8.CrossRefPubMed Ghobrial IM, Fonseca R, Greipp PR, Blood E, Rue M, Vesole DH, et al. Initial immunoglobulin M ‘flare’ after rituximab therapy in patients diagnosed with Waldenström macroglobulinemia: an Eastern Cooperative Oncology Group Study. Cancer. 2004;101:2593–8.CrossRefPubMed
27.
go back to reference Matutes E. Splenic marginal zone lymphoma disease features and management. Expert Rev Hematol. 2013;6:735–45.CrossRefPubMed Matutes E. Splenic marginal zone lymphoma disease features and management. Expert Rev Hematol. 2013;6:735–45.CrossRefPubMed
28.
29.
go back to reference Maevis V, Mey U, Schmidt-Wolf G, Schmidt-Wolf IG. Hairy cell leukemia: short review, today's recommendations and outlook. Blood Cancer J. 2014;4, e184.CrossRefPubMedPubMedCentral Maevis V, Mey U, Schmidt-Wolf G, Schmidt-Wolf IG. Hairy cell leukemia: short review, today's recommendations and outlook. Blood Cancer J. 2014;4, e184.CrossRefPubMedPubMedCentral
Metadata
Title
Superior efficacy of rituximab-based chemoimmunotherapy as an initial therapy in newly diagnosed patients with B cell indolent lymphomas: long-term results from a single center in China
Authors
Zengjun Li
Fei Li
Shuhua Yi
Zhimin Gu
Zhen Yu
Yan Xu
Xiaoyan Feng
Wei Liu
Dehui Zou
Junyuan Qi
Fenghuang Zhan
Lugui Qiu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1534-0

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine