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Meta-Analysis
. 2007 Oct 17;2007(4):CD003805.
doi: 10.1002/14651858.CD003805.pub2.

Chemotherapy plus Rituximab versus chemotherapy alone for B-cell non-Hodgkin's lymphoma

H Schulz  1 , J Bohlius, N Skoetz, S Trelle, T Kober, M Reiser, M Dreyling, M Herold, G Schwarzer, M Hallek, A Engert
Affiliations
Meta-Analysis

Chemotherapy plus Rituximab versus chemotherapy alone for B-cell non-Hodgkin's lymphoma

H Schulz et al. Cochrane Database Syst Rev. .

Abstract

Background: Rituximab has been shown to improve response rates and progression free survival when added to chemotherapy in patients with indolent and mantle cell lymphoma. However, the impact of R on overall survival (OS) when given in combination with chemotherapy (R-chemo) has remained unclear so far.

Objectives: We thus performed a comprehensive systematic review in this group of patients to compare R-chemo with chemotherapy alone with respect to OS. Other endpoints were overall response rate (ORR), toxicity and disease control as assessed by measures such as time to treatment failure (TTF), event free-survival (EFS), progression free-survival (PFS) and time to progression (TTP).

Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and conference proceeding from 1990 to 2005.

Selection criteria: Only randomised controlled trials (RCT) comparing R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed indolent lymphoma and mantle cell lymphoma (MCL) were included.

Data collection and analysis: Two review authors extracted data and assessed the study quality. Number needed to treat (NNT) were calculated to facilitate interpretation.

Main results: Seven randomised controlled trials involving 1943 patients with follicular lymphoma, mantle cell lymphoma, or other indolent lymphomas were included in the meta-analysis. Five studies were published as full-text articles, and two were in abstract form. Patients treated with R-chemo had better overall survival (hazard ratio [HR] for mortality 0.65; 95% confidence interval (CI) 0.54 to 0.78), overall response (relative risk of tumour response 1.21; 95% CI 1.16 to 1.27), and disease control (HR of disease event 0.62; 95% CI 0.55 to 0.71) than patients treated with chemotherapy alone. R-chemo improved overall survival in patients with follicular lymphoma (HR for mortality 0.63; 95% CI 0.51 to 0.79) and in patients with mantle cell lymphoma (HR for mortality 0.60; 95% CI 0.37 to 0.98). However, in the latter case, there was heterogeneity among the trials (P 0.07), making the survival benefit less reliable.

Authors' conclusions: The systematic review demonstrated improved OS for patients with indolent lymphoma, particularly in the subgroups of follicular and in mantle cell lymphoma when treated with R-chemo compared to chemotherapy alone.

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Conflict of interest statement

Thilo Kober was up to March 2006 the co‐ordinator of the Cochrane Haematological Malignancies Group (CHMG) and was involved in the preparation of systematic reviews and other material for the Cochrane Library. Julia Bohlius is a medical officer and reviewer, Andreas Engert is the CHMG co‐ordinating editor and Holger Schulz is a medical officer and reviewer in the CHMG editorial base. All are or were involved in the preparation of systematic reviews. This protocol is not supported by the pharmaceutical industry or by any grant. J. Bohlius gave two presentations on erythropoiesis‐stimulating agents at Hoffmann‐La Roche & Co, the manufacturer of rituximab. M. Reiser, M. Herold, M. Dreyling, and M. Hallek have conducted research sponsored by Hoffmann‐La Roche & Co, the manufacturer of rituximab. M. Herold is a member of the Hoffmann‐La Roche & Co Speaker's bureau, and M. Dreyling has received a speaker's honorarium from Hoffmann‐La Roche & Co. M. Herold is a member of the Hoffmann‐La Roche & Co advisory board. .

Figures

1
1
Forest plot of comparison: 1 Overall survival, outcome: 1.1 Overall survival Total group.
2
2
Forest plot of comparison: 1 Overall survival, outcome: 1.5 Overall survival untreated vs treated patients.
3
3
Forest plot of comparison: 1 Overall survival, outcome: 1.8 Overall survival_Alloc. concealment.
4
4
Forest plot of comparison: 1 Overall survival, outcome: 1.3 Sensitivity: attrition bias.
5
5
Forest plot of comparison: 1 Overall survival, outcome: 1.7 Overall survival_Full Text vs Abstract Publication.
6
6
Forest plot of comparison: 1 Overall survival, outcome: 1.2 Overall survival FL vs MCL.
7
7
Forest plot of comparison: 2 Disease Control, outcome: 2.1 FFS Total group.
8
8
Forest plot of comparison: 2 Disease Control, outcome: 2.9 FFS_Endpoints according to start of measurement.
9
9
Forest plot of comparison: 2 Disease Control, outcome: 2.2 FFS_FL vs MCL.
10
10
Forest plot of comparison: 3 Overall Response, outcome: 3.1 Overall Response Total Group.
11
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Forest plot of comparison: 4 Complete Response, outcome: 4.1 Complete Response Total Group.
12
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Forest plot of comparison: 3 Overall Response, outcome: 3.2 Overall Response FL vs MCL.
13
13
Forest plot of comparison: 4 Complete Response, outcome: 4.2 Complete Response FL vs MCL.
14
14
Forest plot of comparison: 5 Toxicity Grade 3/4, outcome: 5.1 Adverse events (number of patients).
1.1
1.1. Analysis
Comparison 1 Overall survival, Outcome 1 Overall survival Total group.
1.2
1.2. Analysis
Comparison 1 Overall survival, Outcome 2 Overall survival FL vs MCL.
1.3
1.3. Analysis
Comparison 1 Overall survival, Outcome 3 Sensitivity: attrition bias.
1.4
1.4. Analysis
Comparison 1 Overall survival, Outcome 4 Overall survival_Doxorubicin vs Mitoxantrone.
1.5
1.5. Analysis
Comparison 1 Overall survival, Outcome 5 Overall survival untreated vs treated patients.
1.6
1.6. Analysis
Comparison 1 Overall survival, Outcome 6 Overall survival_Anthracylin vs no‐Anthracylin treatment.
1.7
1.7. Analysis
Comparison 1 Overall survival, Outcome 7 Overall survival_Full Text vs Abstract Publication.
1.8
1.8. Analysis
Comparison 1 Overall survival, Outcome 8 Overall survival_Alloc. concealment.
1.9
1.9. Analysis
Comparison 1 Overall survival, Outcome 9 Overall Survival _with or without second randomisation.
2.1
2.1. Analysis
Comparison 2 Disease Control, Outcome 1 FFS Total group.
2.2
2.2. Analysis
Comparison 2 Disease Control, Outcome 2 FFS_FL vs MCL.
2.3
2.3. Analysis
Comparison 2 Disease Control, Outcome 3 FFS_Sensitivity: attrition bias.
2.4
2.4. Analysis
Comparison 2 Disease Control, Outcome 4 Disease control_Doxorubicin vs Mitoxantrone.
2.5
2.5. Analysis
Comparison 2 Disease Control, Outcome 5 Disease control_untreated vs treated patients.
2.6
2.6. Analysis
Comparison 2 Disease Control, Outcome 6 Disease control_Anthracylin vs no‐Anthracylin treatment.
2.7
2.7. Analysis
Comparison 2 Disease Control, Outcome 7 Disease control_Full text vs abstract publication.
2.8
2.8. Analysis
Comparison 2 Disease Control, Outcome 8 FFS_Sensitivity: Alloc. concealment.
2.9
2.9. Analysis
Comparison 2 Disease Control, Outcome 9 FFS_Endpoints according to start of measurement.
2.10
2.10. Analysis
Comparison 2 Disease Control, Outcome 10 FFS_Endpoints TTP, EFS, TTF, PFS.
3.1
3.1. Analysis
Comparison 3 Overall Response, Outcome 1 Overall Response Total Group.
3.2
3.2. Analysis
Comparison 3 Overall Response, Outcome 2 Overall Response FL vs MCL.
3.3
3.3. Analysis
Comparison 3 Overall Response, Outcome 3 Sensitivity: attrition bias.
3.4
3.4. Analysis
Comparison 3 Overall Response, Outcome 4 Overall Response_Doxorubicin vs Mitoxantrone.
3.5
3.5. Analysis
Comparison 3 Overall Response, Outcome 5 Overall Response_untreated vs treated patients.
3.6
3.6. Analysis
Comparison 3 Overall Response, Outcome 6 Overall response_Anthracyclin vs no‐Anthracyclin treatment.
3.7
3.7. Analysis
Comparison 3 Overall Response, Outcome 7 Overall Response_Full text vs Abstract publication.
3.8
3.8. Analysis
Comparison 3 Overall Response, Outcome 8 Overall Response Allocation concealment.
4.1
4.1. Analysis
Comparison 4 Complete Response, Outcome 1 Complete Response Total Group.
4.2
4.2. Analysis
Comparison 4 Complete Response, Outcome 2 Complete Response FL vs MCL.
4.3
4.3. Analysis
Comparison 4 Complete Response, Outcome 3 Complete Response_Doxorubicine vs Mitoxantrone.
4.4
4.4. Analysis
Comparison 4 Complete Response, Outcome 4 Complete Response_anthracycline vs no anthracyclin treatment.
4.5
4.5. Analysis
Comparison 4 Complete Response, Outcome 5 Complete Response _untreated vs treated patients.
5.1
5.1. Analysis
Comparison 5 Toxicity Grade 3/4, Outcome 1 Adverse events (number of patients).
See this image and copyright information in PMC

Update of

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References to ongoing studies

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