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

Blood. 1993 May 1;81(9):2263-71.

Abstract

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Anti-Idiotypic / blood
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal / toxicity
  • Bone Marrow Transplantation*
  • Combined Modality Therapy
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / isolation & purification
  • Enzyme-Linked Immunosorbent Assay
  • Follow-Up Studies
  • Humans
  • Immunotoxins / blood
  • Immunotoxins / therapeutic use
  • Immunotoxins / toxicity*
  • Lymphoma, B-Cell / therapy*
  • 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

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • DNA, Neoplasm
  • Immunotoxins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Ricin
  • Protein-Tyrosine Kinases