title: First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial.
abstract: Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules. In a phase 1/2 trial evaluating safety and efficacy of ofatumumab in relapsed or refractory follicular non-Hodgkin lymphoma (FL) grade 1 or 2, 4 dose groups of 10 patients received 4 weekly infusions of 300, 500, 700, or 1000 mg. Patients had a median of 2 prior FL therapies and 13% had elevated lactate dehydrogenase. No safety concerns or maximum tolerated dose was identified. A total of 274 adverse events were reported; 190 were judged related to ofatumumab, most occurring on the first infusion day with Common Terminology Criteria grade 1 or 2. Eight related events were grade 3. Treatment caused immediate and profound B-cell depletion, and 65% of patients reverted to negative BCL2 status. Clinical response rates ranged from 20% to 63%. Median time to progression for all patients/responders was 8.8/32.6 months, and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months. Ofatumumab is currently being evaluated in patients with rituximab-refractory FL. This trial was registered at www.clinicaltrials.gov as #NCT00092274.
authors.affiliation: University Medical Center Utrecht, Department of Hematology, Utrecht, The Netherlands. a.hagenbeek@umcutrecht.nl
authors.forename: Anton
authors.initials: A
authors.lastname: Hagenbeek
authors.forename: Ole
authors.initials: O
authors.lastname: Gadeberg
authors.forename: Peter
authors.initials: P
authors.lastname: Johnson
authors.forename: Lars Møller
authors.initials: LM
authors.lastname: Pedersen
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Marek
authors.initials: M
authors.lastname: Wojtukiewicz
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Mimi
authors.initials: M
authors.lastname: Flensburg
authors.forename: Jørgen
authors.initials: J
authors.lastname: Petersen
authors.forename: Nedjad
authors.initials: N
authors.lastname: Losic
authors.forename: John
authors.initials: J
authors.lastname: Radford
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007239:Infections / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; C527517:ofatumumab