A systematic review and meta-analysis of immunochemotherapy with rituximab for B-cell non-Hodgkin's lymphoma

Figures & data

Figure 1. Flow chart showing the progress of trials through the review (RCT: randomized controlled trials).

Table I. Summary of trials included in the meta-analysis.*

First author	Lymphoma subtype	Quality scores	Study arms	Total patients	Eligible patients	Previous therapy	Stage	Observation time (mo)	Intent-to treatment	Allocation concealed	Dropouts (%)	Source of data
Coiffier[16]	DLBCL	3	R-CHOP CHOP	399	399	No	III/IV	24	Yes	A	4	Full text
Forstpo miner[17]	FL/MCL	3	R-FCM FCM	147	128	Yes	III/IV	18	Yes	A	13	Full text
Habermann[18]	DLBCL	3	R-CHOP CHOP	632	546	No	III/IV	42	Yes	A	3	Full text
Herold[19]	FL/MCL	3	R-MCP MCP	358	358	No	III/IV	19	Yes	A	0	Abstract
Hiddemann[20]	FL	3	R-CHOP CHOP	428	428	No	III/IV	18	Yes	A	0	Full text
Lenz[21]	MCL	3	R-CHOP CHOP	128	122	No	III/IV	18	Yes	U	5	Full text
Lin[16]	DLBCL	2	R-CHOP CHOP	63	63	No	II/III/IV	NA	Yes	U	6	Full text
Marcus[23]	FL	3	R-CVP CVP	362	361	No	III/IV	30	Yes	A	1	Full text
Pfreundschuh[24]	DLBCL	3	R-CHOP like CHOP like	824	823	No	II/III/IV	34	Yes	A	1	Full text
Rivas-vera[25]	FL	3	R-CNOP CNOP	121	121	No	III/IV	18	U	u	6	Abstract
Van Oers[26]	FL	3	R-CHOP CHOP	474	464	Yes	III/IV	39	Yes	A	0	Full text
Pfreundschuh[27]	NS	3	R-CHOP CHOP	1242	1222	No	II/III/IV	34	Yes	A	4	Full text

*Quality scores of Jadad scores; DLBCL = Diffuse Large B-cell Lymphoma; FL = Follicular Lymphoma; MCL = Mantle Cell Lymphoma; NS = Not specified subtype of B-cell lymphoma; §R=rituximab; CHOP = cyclophosphamide, doxorubicin, vincristine and prednisone; FCM = fludarabine, cyclophosphamide and mitoxantrone; MCP = mitoxantrone, chlorambucil and prednisolone; CVP = cyclophosphamide, vincristine and prednisone; CNOP = cyclophosphamide, mitoxantrone, vincristine and prednisone; CHOEP = cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone; MACOP-B = methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin; PMtCEBO ˆprednisone, mitoxantrone, cyclophosphamide, etoposide, bleomycin and vincristine; CHOP like = CHOP or CHOEP or MACOP-B or PMtCEBO; A = adequate; U = unclear.

Figure 2. Meta-analysis of overall survival among patients receiving rituximab with chemotherapy (R-chemo) or chemotherapy alone. n = number of events; N = number of patients; 95% CI = 95% confidence interval; RR = relative risks; The diamond shows the 95% confidence intervals for the pooled relative risks. Values greater than 1.0 indicate relative risks that favor R-chemo.

Figure 3. Overall survival for the subgroups of patients with diffuse large B-cell lymphoma, mantle cell lymphoma or follicular lymphoma receiving rituximab with chemotherapy (R-chemo) or chemotherapy alone. n = number of events; N = number of patients; 95% CI = 95% confidence interval; RR = relative risks; The diamond shows the 95% confidence intervals for the pooled relative risks. Values greater than 1.0 indicate relative risks that favor R-chemo.

Figure 4. Meta-analysis of overall response rate for patients receiving rituximab with chemotherapy (R-chemo) or chemotherapy alone. n = number of events; N = number of patients; 95% CI = 95% confidence interval; RR ˆrelative risks; The diamond shows the 95% confidence intervals for the pooled relative risks. Values greater than 1.0 indicate relative risks that favor R-chemo.

Figure 5. Meta-analysis of complete response for patients receiving rituximab with chemotherapy (R-chemo) or chemotherapy alone. n = number of events; N = number of patients; 95% CI = 95% confidence interval; RR = relative risks; The diamond shows the 95% confidence intervals for the pooled relative risks. Values greater than 1.0 indicate relative risks that favor R-chemo.

Figure 6. Overall response rate for the subgroups of patients with diffuse large B-cell lymphoma, mantle cell lymphoma or follicular lymphoma receiving rituximab with chemotherapy (R-chemo) or chemotherapy alone. n ˆnumber of events; N ˆnumber of patients; 95% CI = 95% confidence interval; RR = relative risks; The diamond shows the 95% confidence intervals for the pooled relative risks. Values greater than 1.0 indicate relative risks that favor R-chemo.

Figure 7. Meta-analysis of disease control for all patients receiving rituximab with chemotherapy (R-chemo) or chemotherapy alone. Disease control is shown as the relative risks (RR) for a disease event (progression, relapse, death). n = number of events; N = number of patients; 95% CI = 95% confidence interval; RR = relative risks; The diamond shows the 95% confidence intervals for the pooled relative risks. Values greater than 1.0 indicate relative risks that favor R-chemo.

Figure 8. Disease control for the subgroups of patients with diffuse large B-cell lymphoma, mantle cell lymphoma or follicular lymphoma receiving rituximab with chemotherapy (R-chemo) or chemotherapy alone. Disease control is shown as the relative risks (RR) for a disease event (progression, relapse, death). n ˆnumber of events; N ˆnumber of patients; 95% CI =95% confidence interval; RR = relative risks; The diamond shows the 95% confidence intervals for the pooled relative risks. Values greater than 1.0 indicate relative risks that favor R-chemo.

Table II. Summary of toxicity meta-analyses of treatment for B-cell lymphoma among patients receiving rituximab with chemotherapy (R-chemo) or chemotherapy alone^*.

Side effect	No. trials (references)	R-chemo	Chemotherapy	OR (95%CI)	P-value
Anemia	3 [18,24,27]	170/1281	159/1294	1.10 (0.87,1.40)	0.42
Leukocytopenia	5 [19,22–24,27]	391/1385	321/1375	1.32 (1.10,1.58)	0.003
Thrombocytopenia	8 [16,18,19,23–27]	139/1921	120/1908	1.17 (0.91,1.52)	0.22
Granulocytopenia	4 [18,24–26]	388/724	367/716	1.19 (0.94,1.51)	0.14
Fever	2 [19,26]	21/249	5/232	4.18 (1.55,11.28)	<0.001
Infection	7 [18,19,23–27]	316/1921	303/1808	1.01 (0.85,1.21)	0.90
Treat-related deaths	6 [16,18,21,24,26,27]	90/1788	83/1789	1.09 (0.80,1.49)	0.58

*Side effects of grade 3 or 4 according to the National Cancer Institute of Canada Common Toxicity Criteria; OR = odds ratio; CI = confidence interval.

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