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Use of an anti-pan T-lymphocyte ricin a chain immunotoxin in steroid-
resistant acute graft-versus-host disease
VS Byers, PJ Henslee, NA Kernan, BR Blazar, R Gingrich, GL Phillips, CF LeMaistre, G Gilliland, JH Antin and P Martin
XOMA Corporation, Berkeley, CA 94710.
Acute steroid-resistant graft-versus-host disease (AGVHD) after allogeneic
bone marrow transplantation is frequently fatal. A new treatment for this
T-lymphocyte-mediated condition uses an immunotoxin, H65-RTA, comprised of
a monoclonal antibody that recognizes the CD5 lymphocyte differentiation
antigen coupled to ricin A chain, a cytotoxic enzyme that inhibits protein
synthesis. The safety and efficacy of this lymphocyte-targeted immunotoxin
was evaluated in patients with severe AGVHD in a phase I-II dose escalation
study with group expansion at the two middle doses. Thirty-four patients
received up to 14 daily intravenous infusions of the immunotoxin. The
principal side effects were constitutional symptoms such as fatigue and
myalgias, and hypoalbuminemia with weight gain was seen at all doses.
Thirty-two patients were evaluated for improvement or resolution of
disease. Durable complete or partial responses were not dose-related and
were seen in 16 patients. Skin GVHD had the highest incidence of response
(73%), although improvement or resolution in gastrointestinal tract (45%)
and liver (28%) GVHD was also noted. Survival in responding patients was
significantly prolonged at all times as compared with those with no
response (P = .03). Treatment was associated with a rapid decrease in
peripheral blood T lymphocytes, which persisted for greater than 1 month
after therapy. Anti-immunotoxin antibodies were seen in 6 of the 23
patients tested; these were of low titer and did not block immunotoxin
binding to T cells. Results of this study indicate that anti-T-lymphocyte
immunotoxins may form a new class of immunosuppressive agents useful in
T-lymphocyte-mediated diseases.
Volume 75,
Issue 7,
pp. 1426-1432,
04/01/1990
Copyright © 1990 by The American Society of Hematology
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