Anti-B4 blocked ricin post chemotherapy in patients with chronic lymphocytic leukemia--long-term follow-up of a monoclonal antibody-based approach to residual disease.
Anti-B4-blocked ricin is an immunotoxin consisting of anti-B4 murine monoclonal antibody and "blocked ricin" toxin. The anti-B4 monoclonal antibody is directed against the CD19 antigen, which is expressed on B-lymphocytes. A phase II study of anti-B4 blocked ricin toxin in patients with B-cell chronic lymphocytic leukemia (CLL) with residual disease after chemotherapy was conducted. Eleven patients received anti-B4 blocked ricin at 30 microg/kg lean body mass (LBM) daily by continuous infusion for 7 days followed with repeat infusion administered at 14-day intervals. No patient achieved an objective response. The major reasons for failure to respond were the presence of adenopathy and residual marrow disease. Three patients achieved immunophenotypic response in marrow and peripheral blood. Three of 6 patients with rearranged IgH and/or Ig kappa were germline after anti-B4 blocked ricin. The median follow-up of surviving patients is 8.6 years. The median survival is 5.8 years (range, 0.0-8.8). All patients have progressed. The median time to progression was 0.8 years (range, 0.3-3.0). Infusion-related toxicities were all grade 1-2. The most common toxicity was transaminitis. Human antimouse antibody (HAMA) and/or human antiricin antibody (HARA) development was documented in 2 patients. Anti-B4 blocked ricin was well tolerated but had limited activity in patients with residual CLL after chemotherapy.
Tsimberidou
Apostolia M
AM
Department of Leukemia, MD Anderson Cancer Center, University of Texas, 1515 Holcombe Boulevard, Unit 428, Houston, TX 77030, USA.
Giles
Francis J
FJ
Kantarjian
Hagop M
HM
Keating
Michael J
MJ
O'Brien
Susan M
SM
D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000970:Antineoplastic Agents / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000188:drug therapy* / Q000276:immunology; D011379:Prognosis; D012074:Remission Induction; D012276:Ricin / Q000276:immunology / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; C117142:anti-B4 blocked ricin immunoconjugate; D012276:Ricin