Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin's lymphoma.
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.
Grossbard
M L
ML
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Gribben
J G
JG
Freedman
A S
AS
Lambert
J M
JM
Kinsella
J
J
Rabinowe
S N
SN
Eliseo
L
L
Taylor
J A
JA
Blättler
W A
WA
Epstein
C L
CL
D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use / Q000633:toxicity; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D000922:Immunotoxins / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity*; D016393:Lymphoma, B-Cell / Q000628:therapy*; D016133:Polymerase Chain Reaction / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D012276:Ricin / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity*; D014182:Transplantation, Autologous
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D000922:Immunotoxins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012276:Ricin; D011505:Protein-Tyrosine Kinases