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A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in
the treatment of B-cell lymphomas resistant to conventional therapy
PL Amlot, MJ Stone, D Cunningham, J Fay, J Newman, R Collins, R May, M McCarthy, J Richardson and V Ghetie
Department of Clinical Immunology, Royal Free Hospital School of Medicine,
London, United Kingdom.
Twenty-six patients, whose B-cell lymphoma had relapsed after conventional
therapies, were treated in a phase I dose escalation study with an
immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:IgG1K)
coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses
of the immunotoxin were infused intravenously at 48- hour intervals. The
peak serum concentration and half-life (T1/2) did not correlate directly
with the dose and averaged 3.8 micrograms/mL and 7.8 hours, respectively.
The main dose-limiting toxicity was caused by the vascular leak syndrome
(VLS) consisting of weight gain, edema, serum albumin decrease, and
critically by pulmonary edema. Myalgia occurred frequently and was only
dose limiting in one patient who developed rhabdomyolysis. The presence of
lymphoma cells in the blood (> or = 10(10)/L) and clinically detectable
splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine
of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA.
There were five partial responses (PR) and one complete response (CR)
lasting 30 to 78 days. High peak concentrations of immunotoxin in the
serum, a long T1/2, and large areas under the curve (AUC) correlated with
both clinical response and toxicity. None of three patients with CD5+
lymphomas (including two CLL patients) had more than mild toxicity or
responded to the immunotoxin.
Volume 82,
Issue 9,
pp. 2624-2633,
11/01/1993
Copyright © 1993 by The American Society of Hematology
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