Treatment of acute graft-versus-host disease with methylprednisolone and cyclosporine with or without an anti-interleukin-2 receptor monoclonal antibody. A multicenter phase III study.

A double-blind, placebo-controlled trial of BT563, including 13 European centers, was initiated in October 1989 to compare the efficacy of the combination of in vivo anti-CD25 mAb (BT 563), cyclosporine, and steroids versus placebo and CSA-steroids in the treatment of grade II and III acute graft-versus-host disease (GVHD). Sixty-nine patients participated in the study, which excluded non-genotypically identical allogeneic bone marrow transplant recipients. No statistically significant differences were observed, clinically or biologically, between the 2 groups before the onset of the treatment. Treatment responses were scored during and after the 3-week treatment period (mAb or placebo). Efficacy was evaluated on days 4, 10, 20, 30, and 60 or on any day the patient's condition was found to be deteriorating. Preceding and systemically untreated GVHD of grade I was observed in 59% of the cases. No statistically clinically significant differences between the 2 groups were observed during or upon completion of treatment in GVHD grade. Nine patients in the placebo group and 6 in the active group were withdrawn of the study. Thirteen of these 15 patients were withdrawn because of failure of GVHD therapy (9 in the placebo group and 4 in the BT563 group). At day 20 after onset of the treatment, the response rate was 63% and 70% for the placebo and BT563 groups, respectively (NS). Probability of survival at 1 year was 59% and 66% (NS) for the placebo and active groups, respectively. In conclusion, despite preliminary promising results in the treatment of steroid-resistant acute GVHD, the role of first-line treatment with an in vivo anti-interleukin-2 receptor mAb remains to be determined.