Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin's lymphoma

• Published in: Blood 1993-05, Vol.81 (9), p.2263-2271
• Main Authors: GROSSBARD, M. L, GRIBBEN, J. G, NADLER, L. M, FREEDMAN, A. S, LAMBERT, J. M, KINSELLA, J, RABINOWE, S. N, ELISEO, L, TAYLOR, J. A, BLÄTTLER, W. A, EPSTEIN, C. L
• Format: Article
• Language: English
• Subjects: Antibodies, Anti-Idiotypic - blood; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal - toxicity; Antineoplastic agents; Biological and medical sciences; Bone Marrow Transplantation; Combined Modality Therapy; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; Enzyme-Linked Immunosorbent Assay; Follow-Up Studies; Humans; Immunotherapy; Immunotoxins - blood; Immunotoxins - therapeutic use; Immunotoxins - toxicity; Lymphoma, B-Cell - therapy; Medical sciences; Pharmacology. Drug treatments; Polymerase Chain Reaction - methods; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogenes; Ricin - blood; Ricin - therapeutic use; Ricin - toxicity; Transplantation, Autologous
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V81.9.2263.2263

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.