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Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous
bone marrow transplantation for patients with B-cell non- Hodgkin's
lymphoma
ML Grossbard, JG Gribben, AS Freedman, JM Lambert, J Kinsella, SN Rabinowe, L Eliseo, JA Taylor, WA Blattler and CL Epstein
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA
02115.
Anti-B-blocked ricin (anti-B4-bR) combines the specificity of the anti- B4
(CD19) monoclonal antibody with the protein toxin "blocked ricin." In
blocked ricin, affinity ligands are attached to the ricin B-chain to
attenuate its lectin binding capacity. In a phase I trial, Anti-B4-bR was
administered by 7-day continuous infusion to 12 patients in complete
remission after autologous bone marrow transplantation (ABMT) for relapsed
B-cell non-Hodgkin's lymphoma (NHL). Patients were treated at 20, 40, and
50 micrograms/kg/d for 7 days. Potentially therapeutic serum levels could
be sustained for 3 to 4 days. The maximum tolerated dose was 40
micrograms/kg/d for 7 days (total 280 micrograms/kg). The dose-limiting
toxicities were reversible grade IV thrombocytopenia and elevation of
hepatic transaminases. Mild capillary leak syndrome was manifested by
hypoalbuminemia, peripheral edema (4 patients), and dyspnea (1 patient).
Anti-immunotoxin antibodies developed in 7 patients. Eleven patients remain
in complete remission between 13 and 26 months post-ABMT (median 17
months). These results show that Anti-B4- bR can be administered with
tolerable, reversible toxicities to patients with B-cell NHL in complete
remission following ABMT.
Volume 81,
Issue 9,
pp. 2263-2271,
05/01/1993
Copyright © 1993 by The American Society of Hematology
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