Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1-2 clinical trial.
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.
Unité d'Immunologie et d'Hématologie Pédiatriques, Service de Réanimation Pédiatrique and INSERM U429, Hôpital Necker Enfants-Malades, Paris, France. elie.haddad@rdb.ap-hop-paris.fr
E
E
Haddad
S
S
Paczesny
V
V
Leblond
J M
JM
Seigneurin
M
M
Stern
A
A
Achkar
M
M
Bauwens
V
V
Delwail
D
D
Debray
C
C
Duvoux
P
P
Hubert
B
B
Hurault de Ligny
J
J
Wijdenes
A
A
Durandy
A
A
Fischer
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency; D016378:Tissue Transplantation / Q000009:adverse effects; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015850:Interleukin-6; D002097:C-Reactive Protein