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Evaluation of a CD5-specific immunotoxin for treatment of acute graft-
versus-host disease after allogeneic marrow transplantation
PJ Martin, BJ Nelson, FR Appelbaum, C Anasetti, HJ Deeg, JA Hansen, GB McDonald, RA Nash, KM Sullivan, RP Witherspoon, PJ Scannon, N Friedmann and R Storb
Division of Clinical Research, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104, USA.
Acute graft-versus-host disease (GVHD) is most often treated with high dose
glucocorticoids, but less than half of patients have durable overall
improvement. Previous phase I and phase II studies suggested that treatment
with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate
symptoms of GVHD. In a randomized, double-blind trial, we compared
XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids 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 were treated concomitantly with a
standard regimen of methylprednisolone. At the time of entry on study, 94%
of patients had a rash, 56% had hyperbilirubinemia, 61% had diarrhea, and
84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment,
symptom severity was less in the CD5 group than in the placebo group. At 4
weeks, 40% of patients 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 with 38% in the placebo group (P = .36). Clinical extensive
chronic GVHD developed in 65% of patients in the CD5 group compared with
72% in the control group (P = .35). Survival at 1 year after treatment was
49% in the CD5 group and 45% in the control group (P = .68). Side effects
required close monitoring and appropriate adjustment of treatment. The
combined administration of a CD5-specific immunotoxin and glucocorticoids
controls GVHD manifestations more effectively than treatment with
glucocorticoids alone during the first 5 weeks after starting treatment.
Use of this immunotoxin does not result in any long-term clinical benefit
for patients with acute GVHD.
Volume 88,
Issue 3,
pp. 824-830,
08/01/1996
Copyright © 1996 by The American Society of Hematology
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