A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease.
Treatment for steroid-resistant acute graft-versus-host disease (GVHD) has had limited success. ABX-CBL is a hybridoma-generated murine IgM monoclonal antibody against the CD147 antigen, weakly expressed on human leukocytes and up-regulated on activated lymphocytes. A prospective, multicenter, open-label, randomized clinical trial comparing ABX-CBL to antithymocyte globulin (ATG) for treatment of steroid-resistant acute GVHD was conducted in 95 patients at 21 centers. Forty-eight patients received ABX-CBL daily for 14 consecutive days followed by up to 6 weeks of ABX-CBL twice weekly. Forty-seven patients received equine ATG, 30 mg/kg every other day for a total of 6 doses with additional courses as needed. By day 180, overall improvement was similar in the patients receiving ABX-CBL and in those receiving ATG (56% versus 57%, P = .91). Patient survival at 18 months was less favorable on ABX-CBL than on ATG (35% versus 45%), with the 95% confidence interval ruling out that ABX-CBL provides at least a 10.4% improvement. Data from this trial suggest that ABX-CBL does not offer an improvement over ATG in the treatment of acute steroid-resistant GVHD. This prospective, multicenter, randomized clinical trial for steroid-resistant acute GVHD serves as a model for future evaluation of new agents.
Macmillan
Margaret L
ML
Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA. macmi002@umn.edu
Couriel
Daniel
D
Weisdorf
Daniel J
DJ
Schwab
Gisela
G
Havrilla
Nancy
N
Fleming
Thomas R
TR
Huang
Saling
S
Roskos
Lorin
L
Slavin
Shimon
S
Shadduck
Richard K
RK
Dipersio
John
J
Territo
Mary
M
Pavletic
Steve
S
Linker
Charles
C
Heslop
Helen E
HE
Deeg
H Joachim
HJ
Blazar
Bruce R
BR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D051926:Basigin / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D013256:Steroids / Q000494:pharmacology*; D015996:Survival Rate; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; C497886:BSG protein, human; D013256:Steroids; D051926:Basigin