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 language | English (US) |
|---|---|
| Pages (from-to) | 1590-1597 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 97 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2001 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients
T2 - A multicenter phase 1-2 clinical trial
AU - Haddad, Elie
AU - Paczesny, Sophie
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
AU - Durandy, Anne
AU - Fischer, Alain
PY - 2001/3/15
Y1 - 2001/3/15
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035869536&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035869536&partnerID=8YFLogxK
U2 - 10.1182/blood.V97.6.1590
DO - 10.1182/blood.V97.6.1590
M3 - Article
C2 - 11238096
AN - SCOPUS:0035869536
VL - 97
SP - 1590
EP - 1597
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -