EVALUATION OF A CD5-SPECIFIC IMMUNOTOXIN FOR TREATMENT OF ACUTE GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC MARROW TRANSPLANTATION

Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, hue less than half of patients have durable ove rall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could a meliorate symptoms of GVHD. In a randomized, double-blind trial, we co mpared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucoc orticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation. The study drug (XomaZyme CD5 -Plus or an identical appearing placebo) was administered at a dose of 0.1 mg/kg body weight on each of 14 consecutive days. All patients we re treated concomitantly with a standard regimen of methylprednisolone . At the rime of entry on study, 94% of patients had a rash, 56% had h yperbilirubinemia, 61% had diarrhea, and 84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment, symptom severity was le ss in the CD5 group than in the placebo group. At 4 weeks, 40% of pati ents assigned to the CD5 group had complete response compared with 25% of those assigned to the control group (P =.019). At 6 weeks, 44% of patients assigned to the CD5 group had complete response as compared w ith 38% in the placebo group (P =.36). Clinical extensive chronic GVHD developed in 65% of patients in the CD5 group compared with 72% in th e control group (P =.35). Survival at 1 year after treatment was 49% i n the CD5 group and 45% in the control group (P =.68). Side effects re quired close monitoring and appropriate adjustment of treatment. The c ombined administration of a CD5-specific immunotoxin and glucocorticoi ds controls GVHD manifestations more effectively than treatment with g lucocorticoids alone during the first 5 weeks after starting treatment . Use of this immunotoxin does not result in any long-term clinical be nefit for patients with acute GVHD. (C) 1996 by The American Society o f Hematology.