Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: A multicenter phase 1-2 clinical trial

Elie Haddad, Sophie Paczesny, Veronique Leblond, Jean Marie Seigneurin, Marc Stern, Antoine Achkar, Marc Bauwens, Vincent Delwail, Dominique Debray, Christophe Duvoux, Philippe Hubert, Bruno Hurault De Ligny, John Wijdenes, Anne Durandy, Alain Fischer

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.

Original languageEnglish (US)
Pages (from-to)1590-1597
Number of pages8
JournalBlood
Volume97
Issue number6
DOIs
StatePublished - Mar 15 2001
Externally publishedYes

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Clinical Trials, Phase I
Lymphoproliferative Disorders
Interleukin-6
Antibodies
Patient treatment
Therapeutics
T-cells
Viruses
Refractory materials
C-Reactive Protein
Bone
Cells
Disease Progression
Recurrence
Bone Marrow Transplantation
Human Herpesvirus 4

ASJC Scopus subject areas

  • Hematology

Cite this

Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients : A multicenter phase 1-2 clinical trial. / Haddad, Elie; Paczesny, Sophie; Leblond, Veronique; Seigneurin, Jean Marie; Stern, Marc; Achkar, Antoine; Bauwens, Marc; Delwail, Vincent; Debray, Dominique; Duvoux, Christophe; Hubert, Philippe; Hurault De Ligny, Bruno; Wijdenes, John; Durandy, Anne; Fischer, Alain.

In: Blood, Vol. 97, No. 6, 15.03.2001, p. 1590-1597.

Research output: Contribution to journalArticle

Haddad, E, Paczesny, S, Leblond, V, Seigneurin, JM, Stern, M, Achkar, A, Bauwens, M, Delwail, V, Debray, D, Duvoux, C, Hubert, P, Hurault De Ligny, B, Wijdenes, J, Durandy, A & Fischer, A 2001, 'Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: A multicenter phase 1-2 clinical trial', Blood, vol. 97, no. 6, pp. 1590-1597. https://doi.org/10.1182/blood.V97.6.1590
Haddad, Elie ; Paczesny, Sophie ; Leblond, Veronique ; Seigneurin, Jean Marie ; Stern, Marc ; Achkar, Antoine ; Bauwens, Marc ; Delwail, Vincent ; Debray, Dominique ; Duvoux, Christophe ; Hubert, Philippe ; Hurault De Ligny, Bruno ; Wijdenes, John ; Durandy, Anne ; Fischer, Alain. / Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients : A multicenter phase 1-2 clinical trial. In: Blood. 2001 ; Vol. 97, No. 6. pp. 1590-1597.
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abstract = "Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.",
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AU - Leblond, Veronique

AU - Seigneurin, Jean Marie

AU - Stern, Marc

AU - Achkar, Antoine

AU - Bauwens, Marc

AU - Delwail, Vincent

AU - Debray, Dominique

AU - Duvoux, Christophe

AU - Hubert, Philippe

AU - Hurault De Ligny, Bruno

AU - Wijdenes, John

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AU - Fischer, Alain

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N2 - Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.

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