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Risk of infection in patients with lymphoma receiving rituximab: systematic review and meta-analysis.

Lanini S, Molloy AC, Fine PE, Prentice AG, Ippolito G, Kibbler CC - BMC Med (2011)

Bottom Line: Several relevant results have emerged.However, data on special groups of patients (for example, HIV positive subjects and HBV carriers) are lacking.In our opinion more studies are needed to explore the potential effect of R on silent and chronic viral infections.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute for Infectious Diseases, INMI-Lazzaro Spallanzani Via Portuense, 292 00149 Rome, Italy. simone.lanini@inmi.it

ABSTRACT

Background: The addition of Rituximab (R) to standard chemotherapy (C) has been reported to improve the end of treatment outcome in patients affected by CD-20 positive malignant lymphomas (CD20+ ML). Nevertheless, given the profound and prolonged immunosuppression produced by R there are concerns that severe infections may arise. A systematic review and meta-analysis were performed to determine whether or not the addition of R to C may increase the risk of severe infections in adults undergoing induction therapy for CD20+ ML.

Methods: Only randomised controlled trials comparing R-C to C standard alone in adult patients with CD20+ ML were included. Meta-analysis was performed on overall incidence of severe infection, risk of dying as the consequence of infection, risk of febrile neutropenia, risk of severe leucopenia, risk of severe granulocytopenia and overall response assuming a fixed effect model. Heterogeneity was investigated, if present and I2 >20%, according to several predefined baseline characteristics of the study populations.

Results: Several relevant results have emerged. First, the addition of R to standard C does not increase the overall risk of severe infections (RR = 1.00; 95% CI 0.87 to 1.14) nor does it increase the risk of dying as a consequence of infection (RR = 1.60; 95% CI 0.68 to 3.75). Second, we confirmed that the addition of R to standard C increases the proportion of overall response (RR = 1.12; 95% CI 1.09 to 1.15), but it also increases the risk of severe leucopenia (RR = 1.24; 95% CI 1.12 to 1.37) and granulocytopenia (RR = 1.07; 95% CI 1.02 to 1.12).

Conclusions: R-C is superior to standard C in terms of overall response and it does not increase the overall incidence of severe infection. However, data on special groups of patients (for example, HIV positive subjects and HBV carriers) are lacking. In our opinion more studies are needed to explore the potential effect of R on silent and chronic viral infections.

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Fixed-effect model meta-analysis. This figure shows the fixed-effect model meta-analysis of the six outcomes included in the meta-analyses. A) Studies for risk of grade 3 and 4 infections (as shown by the diamond at the bottom) show no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%). B) Three studies for risk of death as a consequence of infection; no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%) was found. C). Eight studies for risk of grade 3 and 4 granulocytopenia; significant evidence for increased risk in R-C vs. C was found, although moderate evidence of heterogeneity (I-squared = 20% to 50%) was present. D) Eight studies for risk of grade 3 and 4 leucopenia; significant evidence for increased risk in R-C vs. C was found, although moderate evidence of heterogeneity (I-squared = 20% to 50%) was present. E). Two studies for risk of febrile neutropenia; no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%) was found. F) Fourteen studies for overall response; overall response was significantly better in R-C vs. C, although strong evidence of heterogeneity (I-squared = >50%) was present. RR = risk ratio, 95% CI = 95% confidence interval.
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Figure 2: Fixed-effect model meta-analysis. This figure shows the fixed-effect model meta-analysis of the six outcomes included in the meta-analyses. A) Studies for risk of grade 3 and 4 infections (as shown by the diamond at the bottom) show no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%). B) Three studies for risk of death as a consequence of infection; no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%) was found. C). Eight studies for risk of grade 3 and 4 granulocytopenia; significant evidence for increased risk in R-C vs. C was found, although moderate evidence of heterogeneity (I-squared = 20% to 50%) was present. D) Eight studies for risk of grade 3 and 4 leucopenia; significant evidence for increased risk in R-C vs. C was found, although moderate evidence of heterogeneity (I-squared = 20% to 50%) was present. E). Two studies for risk of febrile neutropenia; no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%) was found. F) Fourteen studies for overall response; overall response was significantly better in R-C vs. C, although strong evidence of heterogeneity (I-squared = >50%) was present. RR = risk ratio, 95% CI = 95% confidence interval.

Mentions: Figure 2 shows the forest plots with results of the meta-analyses. In particular, pooled RRs did not indicate increased risk in patients receiving R-C compared to those receiving C for infections (RR = 1.00; CI 95% = 0.87 to 1.14, P = 0.943), risk of death as a consequence of infection (RR = 1.60; CI 95% = 0.68 to 3.75, P = 0.279) and febrile neutropenia (RR = 1.14; CI 95% = 0.80 to 1.63; P = 0.478). In contrast, the pooled RRs for risk of leucopenia (RR = 1.24; CI 95% = 1.12 to 1.37; P < 0.001), granulocytopenia (RR = 1.07; CI 95% 1.02 to 1.12; P = 0.008) and overall response (1.12, 95% CI 1.09 to 1.15 P < 0.001) indicated that patients receiving R-C had a greater risk of toxic effects, but a better end of treatment outcome, than patients in C arm.


Risk of infection in patients with lymphoma receiving rituximab: systematic review and meta-analysis.

Lanini S, Molloy AC, Fine PE, Prentice AG, Ippolito G, Kibbler CC - BMC Med (2011)

Fixed-effect model meta-analysis. This figure shows the fixed-effect model meta-analysis of the six outcomes included in the meta-analyses. A) Studies for risk of grade 3 and 4 infections (as shown by the diamond at the bottom) show no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%). B) Three studies for risk of death as a consequence of infection; no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%) was found. C). Eight studies for risk of grade 3 and 4 granulocytopenia; significant evidence for increased risk in R-C vs. C was found, although moderate evidence of heterogeneity (I-squared = 20% to 50%) was present. D) Eight studies for risk of grade 3 and 4 leucopenia; significant evidence for increased risk in R-C vs. C was found, although moderate evidence of heterogeneity (I-squared = 20% to 50%) was present. E). Two studies for risk of febrile neutropenia; no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%) was found. F) Fourteen studies for overall response; overall response was significantly better in R-C vs. C, although strong evidence of heterogeneity (I-squared = >50%) was present. RR = risk ratio, 95% CI = 95% confidence interval.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094236&req=5

Figure 2: Fixed-effect model meta-analysis. This figure shows the fixed-effect model meta-analysis of the six outcomes included in the meta-analyses. A) Studies for risk of grade 3 and 4 infections (as shown by the diamond at the bottom) show no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%). B) Three studies for risk of death as a consequence of infection; no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%) was found. C). Eight studies for risk of grade 3 and 4 granulocytopenia; significant evidence for increased risk in R-C vs. C was found, although moderate evidence of heterogeneity (I-squared = 20% to 50%) was present. D) Eight studies for risk of grade 3 and 4 leucopenia; significant evidence for increased risk in R-C vs. C was found, although moderate evidence of heterogeneity (I-squared = 20% to 50%) was present. E). Two studies for risk of febrile neutropenia; no evidence for increased risk in R-C vs. C arm and negligible heterogeneity (I-squared <20%) was found. F) Fourteen studies for overall response; overall response was significantly better in R-C vs. C, although strong evidence of heterogeneity (I-squared = >50%) was present. RR = risk ratio, 95% CI = 95% confidence interval.
Mentions: Figure 2 shows the forest plots with results of the meta-analyses. In particular, pooled RRs did not indicate increased risk in patients receiving R-C compared to those receiving C for infections (RR = 1.00; CI 95% = 0.87 to 1.14, P = 0.943), risk of death as a consequence of infection (RR = 1.60; CI 95% = 0.68 to 3.75, P = 0.279) and febrile neutropenia (RR = 1.14; CI 95% = 0.80 to 1.63; P = 0.478). In contrast, the pooled RRs for risk of leucopenia (RR = 1.24; CI 95% = 1.12 to 1.37; P < 0.001), granulocytopenia (RR = 1.07; CI 95% 1.02 to 1.12; P = 0.008) and overall response (1.12, 95% CI 1.09 to 1.15 P < 0.001) indicated that patients receiving R-C had a greater risk of toxic effects, but a better end of treatment outcome, than patients in C arm.

Bottom Line: Several relevant results have emerged.However, data on special groups of patients (for example, HIV positive subjects and HBV carriers) are lacking.In our opinion more studies are needed to explore the potential effect of R on silent and chronic viral infections.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute for Infectious Diseases, INMI-Lazzaro Spallanzani Via Portuense, 292 00149 Rome, Italy. simone.lanini@inmi.it

ABSTRACT

Background: The addition of Rituximab (R) to standard chemotherapy (C) has been reported to improve the end of treatment outcome in patients affected by CD-20 positive malignant lymphomas (CD20+ ML). Nevertheless, given the profound and prolonged immunosuppression produced by R there are concerns that severe infections may arise. A systematic review and meta-analysis were performed to determine whether or not the addition of R to C may increase the risk of severe infections in adults undergoing induction therapy for CD20+ ML.

Methods: Only randomised controlled trials comparing R-C to C standard alone in adult patients with CD20+ ML were included. Meta-analysis was performed on overall incidence of severe infection, risk of dying as the consequence of infection, risk of febrile neutropenia, risk of severe leucopenia, risk of severe granulocytopenia and overall response assuming a fixed effect model. Heterogeneity was investigated, if present and I2 >20%, according to several predefined baseline characteristics of the study populations.

Results: Several relevant results have emerged. First, the addition of R to standard C does not increase the overall risk of severe infections (RR = 1.00; 95% CI 0.87 to 1.14) nor does it increase the risk of dying as a consequence of infection (RR = 1.60; 95% CI 0.68 to 3.75). Second, we confirmed that the addition of R to standard C increases the proportion of overall response (RR = 1.12; 95% CI 1.09 to 1.15), but it also increases the risk of severe leucopenia (RR = 1.24; 95% CI 1.12 to 1.37) and granulocytopenia (RR = 1.07; 95% CI 1.02 to 1.12).

Conclusions: R-C is superior to standard C in terms of overall response and it does not increase the overall incidence of severe infection. However, data on special groups of patients (for example, HIV positive subjects and HBV carriers) are lacking. In our opinion more studies are needed to explore the potential effect of R on silent and chronic viral infections.

Show MeSH
Related in: MedlinePlus