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

M Buyse, P Squifflet, BJ Lange… - Blood, The Journal …, 2011 - ashpublications.org
M Buyse, P Squifflet, BJ Lange, TA Alonzo, RA Larson, JE Kolitz, SL George, CD Bloomfield
Blood, The Journal of the American Society of Hematology, 2011ashpublications.org
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 …
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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