A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support

Annette J. Vangsted, Tobias W. Klausen, Peter GimsingD, Niels F. Andersen, Niels Abildgaard, Henrik Gregersen, Ulla Vogel

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Maintenance therapy with interferon-alpha after high-dose treatment with stem cell support in multiple myeloma has been intensively debated. In this study, we evaluated the response to treatment with interferon-alpha in relation to genetic variation in genes related to inflammation.

    Design and Methods

    In a retrospective study of 296 patients with multiple myelom undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon-alpha as maintenance therapy. We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G for associations with time to treatment failure and overall survival with and without interferon-alpha treatment.

    Results

    The wild type ins-allele of polymorphism NFKBi-94 ins/delATTG was, by multivariate Cox analysis, associated with longer time to treatment failure (p=0.01) and overall survival (p=0.0084) when tested between treatment arms and in the subgroup of patients treated with interferon-alpha the wild type ins-allele was associated with longer overall survival (p=0.002). In the absence of interferon-alpha treatment, there was no association between the polymorphisms and treatment outcome, except for patients homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-alpha.

    Conclusions

    Patients who are homozygous carriers of the wild type ins-allele of the NFKB1 - 94ins/delATTG polymorphism may benefit from treatment with interferon-alpha, in contrast to patients carrying the variant allele. This result may indicate that the effect of interferon-alpha treatment is dependent on the availability of nuclear factor-kappa B and the polymorphism in NFKB1 may, therefore, be a good prognostic marker for multiple myeloma patients on maintenance treatment with interferon-alpha after high-dose therapy. A prospective study of interferon-alpha treatment in relation to NFKB1 -94ins/delATTG is highly warranted.

    OriginalsprogEngelsk
    TidsskriftHaematologica
    Vol/bind94
    Udgave nummer9
    Sider (fra-til)1274-1281
    ISSN0390-6078
    DOI
    StatusUdgivet - 2009

    Citer dette

    Vangsted, Annette J. ; Klausen, Tobias W. ; GimsingD, Peter ; Andersen, Niels F. ; Abildgaard, Niels ; Gregersen, Henrik ; Vogel, Ulla. / A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support. I: Haematologica. 2009 ; Bind 94, Nr. 9. s. 1274-1281.
    @article{77954260f93f11de89af000ea68e967b,
    title = "A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support",
    abstract = "Maintenance therapy with interferon-alpha after high-dose treatment with stem cell support in multiple myeloma has been intensively debated. In this study, we evaluated the response to treatment with interferon-alpha in relation to genetic variation in genes related to inflammation.Design and MethodsIn a retrospective study of 296 patients with multiple myelom undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon-alpha as maintenance therapy. We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G for associations with time to treatment failure and overall survival with and without interferon-alpha treatment.ResultsThe wild type ins-allele of polymorphism NFKBi-94 ins/delATTG was, by multivariate Cox analysis, associated with longer time to treatment failure (p=0.01) and overall survival (p=0.0084) when tested between treatment arms and in the subgroup of patients treated with interferon-alpha the wild type ins-allele was associated with longer overall survival (p=0.002). In the absence of interferon-alpha treatment, there was no association between the polymorphisms and treatment outcome, except for patients homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-alpha.ConclusionsPatients who are homozygous carriers of the wild type ins-allele of the NFKB1 - 94ins/delATTG polymorphism may benefit from treatment with interferon-alpha, in contrast to patients carrying the variant allele. This result may indicate that the effect of interferon-alpha treatment is dependent on the availability of nuclear factor-kappa B and the polymorphism in NFKB1 may, therefore, be a good prognostic marker for multiple myeloma patients on maintenance treatment with interferon-alpha after high-dose therapy. A prospective study of interferon-alpha treatment in relation to NFKB1 -94ins/delATTG is highly warranted.",
    keywords = "polymorphism, multiple myeloma, interferon, NF-kappa B, treatment outcome",
    author = "Vangsted, {Annette J.} and Klausen, {Tobias W.} and Peter GimsingD and Andersen, {Niels F.} and Niels Abildgaard and Henrik Gregersen and Ulla Vogel",
    year = "2009",
    doi = "10.3324/haematol.2008.004572",
    language = "English",
    volume = "94",
    pages = "1274--1281",
    journal = "Haematologica",
    issn = "0390-6078",
    publisher = "Ferrata Storti Foundation",
    number = "9",

    }

    A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support. / Vangsted, Annette J.; Klausen, Tobias W.; GimsingD, Peter; Andersen, Niels F.; Abildgaard, Niels; Gregersen, Henrik; Vogel, Ulla.

    I: Haematologica, Bind 94, Nr. 9, 2009, s. 1274-1281.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support

    AU - Vangsted, Annette J.

    AU - Klausen, Tobias W.

    AU - GimsingD, Peter

    AU - Andersen, Niels F.

    AU - Abildgaard, Niels

    AU - Gregersen, Henrik

    AU - Vogel, Ulla

    PY - 2009

    Y1 - 2009

    N2 - Maintenance therapy with interferon-alpha after high-dose treatment with stem cell support in multiple myeloma has been intensively debated. In this study, we evaluated the response to treatment with interferon-alpha in relation to genetic variation in genes related to inflammation.Design and MethodsIn a retrospective study of 296 patients with multiple myelom undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon-alpha as maintenance therapy. We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G for associations with time to treatment failure and overall survival with and without interferon-alpha treatment.ResultsThe wild type ins-allele of polymorphism NFKBi-94 ins/delATTG was, by multivariate Cox analysis, associated with longer time to treatment failure (p=0.01) and overall survival (p=0.0084) when tested between treatment arms and in the subgroup of patients treated with interferon-alpha the wild type ins-allele was associated with longer overall survival (p=0.002). In the absence of interferon-alpha treatment, there was no association between the polymorphisms and treatment outcome, except for patients homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-alpha.ConclusionsPatients who are homozygous carriers of the wild type ins-allele of the NFKB1 - 94ins/delATTG polymorphism may benefit from treatment with interferon-alpha, in contrast to patients carrying the variant allele. This result may indicate that the effect of interferon-alpha treatment is dependent on the availability of nuclear factor-kappa B and the polymorphism in NFKB1 may, therefore, be a good prognostic marker for multiple myeloma patients on maintenance treatment with interferon-alpha after high-dose therapy. A prospective study of interferon-alpha treatment in relation to NFKB1 -94ins/delATTG is highly warranted.

    AB - Maintenance therapy with interferon-alpha after high-dose treatment with stem cell support in multiple myeloma has been intensively debated. In this study, we evaluated the response to treatment with interferon-alpha in relation to genetic variation in genes related to inflammation.Design and MethodsIn a retrospective study of 296 patients with multiple myelom undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon-alpha as maintenance therapy. We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G for associations with time to treatment failure and overall survival with and without interferon-alpha treatment.ResultsThe wild type ins-allele of polymorphism NFKBi-94 ins/delATTG was, by multivariate Cox analysis, associated with longer time to treatment failure (p=0.01) and overall survival (p=0.0084) when tested between treatment arms and in the subgroup of patients treated with interferon-alpha the wild type ins-allele was associated with longer overall survival (p=0.002). In the absence of interferon-alpha treatment, there was no association between the polymorphisms and treatment outcome, except for patients homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-alpha.ConclusionsPatients who are homozygous carriers of the wild type ins-allele of the NFKB1 - 94ins/delATTG polymorphism may benefit from treatment with interferon-alpha, in contrast to patients carrying the variant allele. This result may indicate that the effect of interferon-alpha treatment is dependent on the availability of nuclear factor-kappa B and the polymorphism in NFKB1 may, therefore, be a good prognostic marker for multiple myeloma patients on maintenance treatment with interferon-alpha after high-dose therapy. A prospective study of interferon-alpha treatment in relation to NFKB1 -94ins/delATTG is highly warranted.

    KW - polymorphism

    KW - multiple myeloma

    KW - interferon

    KW - NF-kappa B

    KW - treatment outcome

    U2 - 10.3324/haematol.2008.004572

    DO - 10.3324/haematol.2008.004572

    M3 - Journal article

    VL - 94

    SP - 1274

    EP - 1281

    JO - Haematologica

    JF - Haematologica

    SN - 0390-6078

    IS - 9

    ER -