Overall Survival of Lymphoma Patients In Randomized Controlled Trials Comparing Primary G-CSF Chemotherapy Support to Control.

Randomized controlled trials (RCTs) have shown that granulocyte colony-stimulating factor (G-CSF) can reduce the risk of neutropenic complications as well as early mortality (Kuderer et al. JCO 2007). The impact of G-CSF support of chemotherapy on overall survival in patients with lymphoma is assessed here in a systematic review of RCTs of chemotherapy with versus without G-CSF in studies with at least 2 years of follow up.

A systematic review of RCTs of patients with malignant lymphoma receiving chemotherapy with versus without primary G-CSF support and reporting overall mortality by study arm identified 16 eligible studies. Data extraction was conducted by two independent reviewers. Heterogeneity was evaluated using Cochran's Q-statistic and the Inconsistency Index (I²). Weighted summary estimates of relative risk (RR) and absolute risk (AR) were based on the method of Mantel and Haenszel. Chemotherapy relative dose intensity (RDI) with G-CSF support compared to control was meta-regressed on the logarithm of RR for mortality. Egger's regression intercept was utilized to assess publication bias.

Sixteen (16) eligible RCTs of patients receiving chemotherapy with (n=2,731) versus without (n=2,757) primary G-CSF support were identified. Deaths were reported in 927 patients randomized to receive primary G-CSF and in 1,064 controls. No significant heterogeneity was observed (Q=12.50, P=.641; I²=0%). Overall RR for mortality with versus without G-CSF support of chemotherapy was 0.876 [95% CI: 0.822 – 0.935; P<.001]. The AR reduction for mortality in G-CSF-supported patients versus control was 4.8% [95% CI: 2.4% - 7.15; P<.001]. An inverse trend was observed between the difference in RDI between treatment arms and RR for mortality [Slope = -0.39; 95% CI: -0.78 – 0.01; P=.057]. The greatest reduction in mortality was observed in the 5 RCTs of dose dense chemotherapy [RR=0.830; 95% CI:0.742-0.930; P=.001]. Significant treatment effect was observed in 7 studies limited to older patients [RR=0.910;95% CI: 0.847–0.978;P=.010] and 9 permitting all adult age groups [RR=0.813;95% CI: 0.715–0.926;P=.002]. No difference in treatment effect was observed based on study funding source and no evidence for publication bias was observed.

A highly significant reduction in overall mortality was associated with G-CSF support compared to control in 16 RCTs of lymphoma patients receiving chemotherapy. Patients receiving greater RDI with G-CSF support, especially those receiving dose dense regimens, experienced the greatest reduction in mortality.

Lyman:Amgen: Research Funding. Crawford:Amgen: Consultancy. Dale:Amgen: Consultancy, Research Funding.