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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.

SUBMITTER: Buyse M

PROVIDER: S-EPMC3539044 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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

Buyse Marc M Squifflet Pierre P Lange Beverly J BJ Alonzo Todd A TA Larson Richard A RA Kolitz Jonathan E JE George Stephen L SL Bloomfield Clara D CD Castaigne Sylvie S Chevret Sylvie S Blaise Didier D Maraninchi Dominique D Lucchesi Kathryn J KJ Burzykowski Tomasz T

Blood 20110425 26

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) ...[more]

PMID: 21518931

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Project description:Before the era of tyrosine kinase inhibitors (TKIs), interferon-alpha (IFN-?) was the treatment of choice in chronic myeloid leukemia (CML). Curiously, some IFN-? treated patients were able to discontinue therapy without disease progression. The aim of this project was to study the immunomodulatory effects of IFN-? in CML patients in prolonged remission and isolate biological markers predicting response. Due to rarity of patients on IFN-? monotherapy, a relatively small cohort of patients still on treatment (IFN-ON, n?=?10, median therapy duration 11.8 years) or had discontinued IFN-? therapy but remained in remission for >2 years (IFN-OFF, n?=?9) were studied. The lymphocyte immunophenotype was analyzed with a comprehensive flow cytometry panel and plasma cytokine levels were measured with multiplex bead-based assay. In addition, the clonality status of different lymphocyte subpopulations was analyzed by TCR ?/? rearrangement assay. Median NK-cell absolute number and proportion from lymphocytes in blood was higher in IFN-OFF patients as compared to IFN-ON patients or controls (0.42, 0.19, 0.21×10(9)/L; 26%, 12%, 11%, respectively, p<0.001). The proportion of CD8+ T-cells was significantly increased in both patient groups and a larger proportion of T-cells expressed CD45RO. Most (95%) patients had significant numbers of oligoclonal lymphocytes characterized by T-cell receptor ?/? rearrangements. Strikingly, in the majority of patients (79%) a distinct clonal V?9 gene rearrangement was observed residing in ??(+) T-cell population. Similar unique clonality pattern was not observed in TKI treated CML patients. Plasma eotaxin and MCP-1 cytokines were significantly increased in IFN-OFF patients. Despite the limited number of patients, our data indicates that IFN-? treated CML patients in remission have increased numbers of NK-cells and clonal ??(+) T-cells and a unique plasma cytokine profile. These factors may relate to anti-leukemic effects of IFN-? in this specific group of patients and account for prolonged therapy responses even after drug discontinuation.

Dataset Information

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

Publications

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

Similar Datasets

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