title: Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin's lymphoma: phase I/II results.
abstract: OBJECTIVE
  This is a multicenter phase I/II dose-finding study in relapsed/refractory B-cell non-Hodgkin's lymphoma (NHL) evaluating veltuzumab, a humanized anti-CD20 antibody with structure-function differences from chimeric rituximab.
  
  
  METHODS
  Eighty-two patients (median age, 64 years; 79% stage III/IV, one to nine prior treatments) received four once-weekly doses of 80 to 750 mg/m(2) of veltuzumab and were assessed for safety, efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity.
  
  
  RESULTS
  Veltuzumab was well tolerated, with no grade 3 to 4 drug-related adverse events despite short infusion times (typically 2 hours initially, 1 hour subsequently at doses < 375 mg/m(2)). In follicular lymphoma, 24 (44%) of 55 patients had objective responses (OR), with 15 (27%) complete responses (CRs) or CRs unconfirmed (CRus) by International Working Group criteria, and with some responses occurring despite two to five prior rituximab-containing regimens, less favorable prognosis (elevated lactate dehydrogenase, tumors > 5 cm, and Follicular Lymphoma International Prognostic Index > or = 2), and at all dose levels. The CRs/CRus were durable (median duration, 19.7 months), with five patients still ongoing (15.9 to 37.6 months duration). In marginal zone lymphoma, five (83%) of six patients had ORs, with two CRs/CRus (33%), and in diffuse large B-cell lymphoma, three (43%) of seven patients achieved partial responses. At all dose levels studied, B cells were depleted after the first infusion, veltuzumab serum half-lives were similar after the fourth infusion, and mean antibody serum levels exceeded values considered important for anti-CD20 therapy (ie, 25 microg/mL).
  
  
  CONCLUSIONS
  Veltuzumab appeared safe and active at all tested doses, encouraging further study, including dose levels less than those typically used with rituximab.
authors.affiliation: Service des Maladies du Sang Centre Hospitalier Regional, Lille, France. f-morschhauser@chru-lille.fr
authors.forename: Franck
authors.initials: F
authors.lastname: Morschhauser
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Luis
authors.initials: L
authors.lastname: Fayad
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Petillon
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Schuster
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Heather
authors.initials: H
authors.lastname: Horne
authors.forename: Nick
authors.initials: N
authors.lastname: Teoh
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011537:Pruritus / Q000139:chemically induced; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C493846:veltuzumab