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Meta-Analysis
. 2011 Jun 30;117(26):7007-13.
doi: 10.1182/blood-2011-02-337725. Epub 2011 Apr 25.

Individual patient data meta-analysis of randomized trials evaluating IL-2 monotherapy as remission maintenance therapy in acute myeloid leukemia

Marc Buyse  1 , Pierre Squifflet, Beverly J Lange, Todd A Alonzo, Richard A Larson, Jonathan E Kolitz, Stephen L George, Clara D Bloomfield, Sylvie Castaigne, Sylvie Chevret, Didier Blaise, Dominique Maraninchi, Kathryn J Lucchesi, Tomasz Burzykowski
Affiliations
Meta-Analysis

Individual patient data meta-analysis of randomized trials evaluating IL-2 monotherapy as remission maintenance therapy in acute myeloid leukemia

Marc Buyse et al. Blood. .

Abstract

IL-2 is a natural, T cell-derived cytokine that stimulates the cytotoxic functions of T and natural killer cells. IL-2 monotherapy has been evaluated in several randomized clinical trials (RCTs) for remission maintenance in patients with acute myeloid leukemia (AML) in first complete remission (CR1), and none demonstrated a significant benefit of IL-2 monotherapy. The objective of this meta-analysis was to reliably determine IL-2 efficacy by combining all available individual patient data (IPD) from 5 RCTs (N = 905) and summary data from a sixth RCT (N = 550). Hazard ratios (HRs) were estimated using Cox regression models stratified by trial, with HR < 1 indicating treatment benefit. Combined IPD showed no benefit of IL-2 over no treatment in terms of leukemia-free survival (HR = 0.97; P = .74) or overall survival (HR = 1.08; P = .39). Analyses including the sixth RCT yielded qualitatively identical results (leukemia-free survival HR = 0.96, P = .52; overall survival HR = 1.06; P = .46). No significant heterogeneity was found between the trials. Prespecified subset analyses showed no interaction between the lack of IL-2 effect and any factor, including age, sex, baseline performance status, karyotype, AML subtype, and time from achievement of CR1 to initiation of maintenance therapy. We conclude that IL-2 alone is not an effective remission maintenance therapy for AML patients in CR1.

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Figures

Figure 1
Figure 1
Forest plots of HRs for the benefit of IL-2 monotherapy in terms of LFS in all 6 RCTs. O/N = event rate per arm where O is the number of observed events (relapse or death) and N is the sample size.
Figure 2
Figure 2
Kaplan-Meier estimates of LFS using IPD from 5 RCTs of IL-2 monotherapy versus control (no treatment).
Figure 3
Figure 3
Forest plots of HRs for the benefit of IL-2 monotherapy in terms of OS in all 6 RCTs. O/N = event rate per arm where O is the number of observed events (relapse or death) and N is the sample size.
Figure 4
Figure 4
Kaplan-Meier estimates of OS using IPD from 5 RCTs of IL-2 monotherapy versus control (no treatment).
See this image and copyright information in PMC

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