A PHASE-II STUDY OF BTI-322, A MONOCLONAL ANTI-CD2 ANTIBODY, FOR TREATMENT OF STEROID-RESISTANT ACUTE GRAFT-VERSUS-HOST DISEASE

BTI-322, a rat monoclonal IgG2b directed against the CD2 antigen on T cells and natural killer (NK) cells, blocks primary and memory alloant igen proliferative responses in vitro. We have evaluated the pharmacok inetics and safety of BTI-322 during treatment of 20 transplant recipi ents with steroid-refractory acute graft-versus-host disease (GVHD). T reatment consisted of BTI-322 by intravenous (IV) bolus or 30-minute i nfusion at approximately 0.1 mg/kg/d for 10 days in addition to contin uing high-dose steroids and tacrolimus or cyclosporine. Pharmacokineti c sampling was performed in 10 patients; the t(1/2) +/- SE was 9.1 +/- 1.3 hours, the C-max was 2,549 +/- 291 ng/mL, the Vd was 3.97 +/- 0.9 5 L, and the Vd/kg was 0.05 +/- 0.01 L/kg. Ten patients experienced tr ansient dyspnea sometimes accompanied by nausea, vomiting, diarrhea, a nd tachycardia shortly after the initial bolus dose of drug, but serio us drug-related adverse events were not seen during the remainder of t he infusions. At the end of treatment (day 11), there were six patient s with complete responses and five with a reduction in grade of GVHD f or a total response rate of 55% (95% confidence interval [CI], 32% to 77%), Antibodies targeting CD2 may be active in the treatment of acute GVHD, and evaluation of a humanized form of BTI-322 is warranted. (C) 1998 by The American Society of Hematology.