title: Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy.
abstract: Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median Cmaxand Ctroughvalues were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher Cmaxand Ctroughvalues at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas ofatumumab pharmacokinetics were not associated with an objective response (OR) on the basis of univariate analyses. Multivariate analyses indicated that baseline patient/disease factors were predominantly associated with CR (17p status) or OR (bulky lymphadenopathy, gender, and serum thymidine kinase), rather than ofatumumab pharmacokinetics.
  
  
  
  www.clinicaltrials.gov (NCT00410163).
authors.affiliation: a Novartis Pharmaceuticals , Morrisville , NC , USA.
authors.forename: Roxanne C
authors.initials: RC
authors.lastname: Jewell
authors.affiliation: b UCSD Moores Cancer Center , La Jolla , CA , USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.affiliation: c Klinik für Hämatologie , Universitätsklinikum Essen , Essen , Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.affiliation: d Vilnius University Hospital Santariskiu Klinikos, Vilnius University , Vilnius , Lithuania.
authors.forename: Laimonas
authors.initials: L
authors.lastname: Griskevicius
authors.affiliation: e Department of Internal Medicine III , Universitätsklinikum Ulm , Ulm , Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: f 4th Department of Internal Medicine - Hematology , University Hospital and Faculty of Medicine , Hradec Králové , Czech Republic.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Smolej
authors.affiliation: g Department of Internal Medicine/Hemato-Oncology , University Hospital Brno , Brno , Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Mayer
authors.affiliation: h Johannes Gutenberg University , Mainz , Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
authors.affiliation: i Roswell Park Cancer Institute , Buffalo , NY , USA.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Hernandez-Ilizaliturri
authors.affiliation: j Cancer Therapy and Research Center , San Antonio , TX , USA.
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Padmanabhan-Iyer
authors.affiliation: k Pharstat Inc. , Raleigh , NC , USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: a Novartis Pharmaceuticals , Morrisville , NC , USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Goldstein
authors.affiliation: l GlaxoSmithKline , Collegeville , PA , USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Gorczyca
authors.affiliation: m Novartis Pharmaceuticals , King of Prussia , PA , USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Gupta
authors.affiliation: n Genmab , Copenhagen , Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Lisby
authors.affiliation: o MD Anderson Cancer Center, The University of Texas , Houston , TX , USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002869:Chromosome Aberrations; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; C527517:ofatumumab
keywords: Chemoimmunotherapy; chronic lymphocytic leukemia; ofatumumab; pharmacokinetics