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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

A systematic review and meta-analysis of rituximab-based immunochemotherapy for subtypes of diffuse large B cell lymphoma

C Fang, W Xu, and JY Li.

Review published: 2010.

Link to full article: [Journal publisher]

CRD summary

The review examined the efficacy of rituximab plus chemotherapy compared with chemotherapy alone in patients with two gene subtypes of diffuse large B cell lymphoma. It concluded that combined rituximab chemotherapy improved survival regardless of disease subtype. Limitations surrounding the meta-analyses and the absence of a quality assessment of included trials indicate that these conclusions should be interpreted with caution.

Authors' objectives

To examine the efficacy of rituximab plus chemotherapy versus chemotherapy alone in patients with two subtypes of diffuse large B cell lymphoma.

Searching

PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched; search terms were not reported. There were no date or language restrictions. Conference proceedings of three relevant societies were searched. It appeared that only published studies were sought.

Study selection

Randomised controlled trials (RCTs) that compared rituximab plus chemotherapy with the same chemotherapy alone in adult populations (older than 18 years) with histological proof of two different subgroups (by immunohistochemistry) regardless of stage of disease or previous treatment were eligible for inclusion. Trials had to study more than 10 patients in each arm. The outcomes of interest were overall survival, overall response, and disease control.

Most included trials used the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (or a CHOP-like regimen). No patients had received previous therapy. All included patients were diagnosed with diffuse large B cell lymphoma by accurate histological diagnosis. Most patients had the germinal centre B cell-like (GCB) subtype.

Two reviewers independently selected studies, with disagreements resolved by a third reviewer.

Assessment of study quality

The authors stated that two reviewers independently evaluated trial quality, but no details of what was assessed were presented.

Data extraction

Two reviewers independently extracted data to calculate relative risks (RRs) and 95% confidence intervals (CIs).

Methods of synthesis

Meta-analyses were performed to calculate pooled relative risks using a fixed-effect model, or a random effects model when evidence of heterogeneity was found. Heterogeneity was evaluated using I2.

Results of the review

Six RCTs (n=748 patients) were included in the review. Follow-up periods ranged from 16 to 76 months.

In patients who received combined rituximab plus chemotherapy, the germinal centre B cell-like (GCB) subtype group had a significantly better overall survival than the non-GCB group (RR 1.16, 95% CI 1.03 to 1.31; I2=0%; five RCTs, n=323 patients), although differences in disease control rates (five RCTs) and overall response (three RCTs) did not reach statistical significance.

Patients who received combined rituximab plus chemotherapy had significantly improved overall survival (GCB subtype RR 1.30, 95% CI 1.11 to 1.51; I2=60%; four RCTs, n=286 patients: non-GCB subtype RR 1.89, 95% CI 1.52 to 2.35; I2=0%; four RCTs, n=328 patients) and disease control rate (GCB subtype RR 1.27, 95% CI 1.05 to 1.54; I2=0%; four RCTs: non-GCB subtype RR 2.21, 95% CI 1.68 to 2.90; I2=0%; , four RCTs) than patients who received chemotherapy alone.

The published forest plots indicated that all results were in the opposite direction to those reported by the authors.

Authors' conclusions

Rituximab plus chemotherapy significantly improved survival in patients with diffuse large B cell lymphoma regardless of the gene subtype.

CRD commentary

The review addressed a clear question and was supported by appropriate inclusion criteria. Attempts to identify relevant studies, in any language, were undertaken by searching databases and checking references and conference proceedings. It appeared that only published studies were sought, so the review may have been subject to publication bias. Suitable methods were employed to reduce the risks of reviewer error and bias throughout the review.

The authors stated that the trials were quality assessed but no further details or results were presented, so it was not possible to evaluate the risk of bias in the included trials. Only basic study details were provided. Some of the subgroup analyses appeared to have been performed using data only from the rituximab plus chemotherapy group, which raised uncertainty about their reliability. Also, when significant heterogeneity was found, the likely causes were not investigated and a fixed-effect model was still used.

The limitations surrounding the meta-analyses and the absence of a trial quality assessment indicate that the authors' conclusions should be interpreted with caution.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that there was a need for further studies of rituximab plus chemotherapy with larger sample sizes to allow gene subtype comparisons.

Funding

National Natural Science Foundation of China.

Bibliographic details

Fang C, Xu W, Li JY. A systematic review and meta-analysis of rituximab-based immunochemotherapy for subtypes of diffuse large B cell lymphoma. Annals of Hematology 2010; 89(11): 1107-1113. [PubMed: 20499236]

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Antibodies, Monoclonal /immunology /therapeutic use; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents /immunology /therapeutic use; Disease-Free Survival; Humans; Immunologic Factors /immunology /therapeutic use; Immunotherapy /methods; Lymphoma, Large B-Cell, Diffuse /drug therapy /immunology; Survival Rate; Treatment Outcome

AccessionNumber

12010007093

Database entry date

30/11/2011

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 20499236

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