title: A Phase II study of adjuvant therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with relapsed B-cell non-Hodgkin's lymphoma.
abstract: This Phase II trial was undertaken to determine the safety, toxicity, and potential efficacy of the B-cell restricted immunotoxin anti-B4-blocked ricin (Anti-B4-bR) when administered as adjuvant therapy to patients in complete remission (CR) after autologous bone marrow transplantation (ABMT) for B-cell non-Hodgkin's lymphoma (NHL). Forty-nine patients with B-cell NHL in CR 46-202 days (median, 112 days) post-ABMT received Anti-B4-bR at a dose of 30 microg/kg lean body weight/day for 7 days by continuous i.v. infusion. Patients were eligible for up to two additional courses of therapy at 14-day intervals. A total of 83 courses of Anti-B4-bR were administered, with 31 patients receiving two or more courses of therapy. The mean serum level on day 7 of the first course was 0.77+/-0.41 nM. Reversible toxicities included hepatic transaminase elevations, thrombocytopenia, myalgias, fatigue, nausea, hypoalbuminemia, and dyspnea. Human antimouse antibody (HAMA) and/or human antiricin antibody (HARA) responses occurred in 23 patients at a median of 22 days from the initiation of Anti-B4-bR therapy (range, 11-100 days). The 4-year disease-free survival and overall survival are estimated at 56 and 72%, respectively. Twenty-six patients remain in CR after a median follow-up of 54.5 months. This study demonstrates that Anti-B4-bR can be administered safely to patients as adjuvant therapy early after ABMT for B-cell NHL. The toxicities are tolerable and reversible. Although the early estimate of disease-free survival was very encouraging in this single-armed trial, the 4-year follow-up data demonstrate continued relapse.
authors.affiliation: Hematology/Oncology Unit, Massachusetts General Hospital, Boston 02114, USA. mgrossbard@partners.org
authors.forename: M L
authors.initials: ML
authors.lastname: Grossbard
authors.forename: P S
authors.initials: PS
authors.lastname: Multani
authors.forename: A S
authors.initials: AS
authors.lastname: Freedman
authors.forename: S
authors.initials: S
authors.lastname: O'Day
authors.forename: J G
authors.initials: JG
authors.lastname: Gribben
authors.forename: C
authors.initials: C
authors.lastname: Rhuda
authors.forename: D
authors.initials: D
authors.lastname: Neuberg
authors.forename: L M
authors.initials: LM
authors.lastname: Nadler
mesh_terms: D000328:Adult; D000910:Antibodies, Heterophile / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000276:immunology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012276:Ricin / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D012276:Ricin