Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147 monoclonal antibody ABX-CBL.
ABX-CBL, an immunoglobulin M murine monoclonal antibody, recognizes CD147 and initiates cell killing through complement-mediated lysis. In a dose-finding trial, 27 patients with steroid-refractory acute graft-versus-host disease (GVHD) received ABX-CBL at 0.01 (presumed no effect dose), 0.1, 0.2, or 0.3 mg/kg per day, and an additional 32 patients were given ABX-CBL at 0.2 or 0.15 mg/kg per day. All patients had undergone allogeneic transplantation for malignant or nonmalignant disorders and received GVHD prophylaxis, generally with methotrexate- and cyclosporine-containing regimens. None responded to methylprednisolone, given for a minimum of 3 days. ABX-CBL was started 20 to 236 (median, 47) days after transplantation; it was given for 7 consecutive days and was followed by 2 infusions per week for 2 more weeks. Among 51 patients evaluable for efficacy, 26 (51%) responded, including 13 with complete responses (CR) and 13 with partial responses (PR). CR lasting 14 days or longer or PR lasting 7 days or longer occurred in 21 (41%; 8 CR, 13 PR) patients, including 19 of 43 (44%) patients who received 0.1 to 0.3 mg/kg ABX-CBL and 2 of 8 (25%) patients given 0.01 mg/kg per day. Myalgias at doses 0.2 mg/kg or greater were dose limiting and resolved without sequelae. Causes of death included organ failure, progressive GVHD, and infection. No death was attributed to ABX-CBL. At 6 months after the initiation of ABX-CBL therapy, 26 (44%) patients were surviving. These results are encouraging. Further studies on the use of ABX-CBL in the management of GVHD are warranted.
Deeg
H J
HJ
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. jdeeg@fhcrc.org
Blazar
B R
BR
Bolwell
B J
BJ
Long
G D
GD
Schuening
F
F
Cunningham
J
J
Rifkin
R M
RM
Abhyankar
S
S
Briggs
A D
AD
Burt
R
R
Lipani
J
J
Roskos
L K
LK
White
J M
JM
Havrilla
N
N
Schwab
G
G
Heslop
H E
HE
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D007223:Infant; D016131:Lymphocyte Subsets; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D013256:Steroids / Q000627:therapeutic use; D016019:Survival Analysis; D013810:Therapeutic Equivalency
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D030161:Avian Proteins; C497886:BSG protein, human; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D008562:Membrane Glycoproteins; D013256:Steroids; D051926:Basigin