title: Individual patient data meta-analysis of randomized trials evaluating IL-2 monotherapy as remission maintenance therapy in acute myeloid leukemia.
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.
authors.affiliation: International Drug Development Institute, Louvain-la-Neuve, Belgium. marc.buyse@iddi.com
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Pierre
authors.initials: P
authors.lastname: Squifflet
authors.forename: Beverly J
authors.initials: BJ
authors.lastname: Lange
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Stephen L
authors.initials: SL
authors.lastname: George
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Sylvie
authors.initials: S
authors.lastname: Castaigne
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.forename: Dominique
authors.initials: D
authors.lastname: Maraninchi
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Lucchesi
authors.forename: Tomasz
authors.initials: T
authors.lastname: Burzykowski
mesh_terms: D000328:Adult; D002648:Child; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000517:prevention & control* / Q000628:therapy; D008297:Male; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D055502:Secondary Prevention; D016019:Survival Analysis
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D011994:Recombinant Proteins