title: Phase III, randomized study of ofatumumab versus physicians' choice of therapy and standard versus extended-length ofatumumab in patients with bulky fludarabine-refractory chronic lymphocytic leukemia.
abstract: We report results of a randomized, phase III study of ofatumumab versus physicians' choice treatment in patients with bulky fludarabine-refractory chronic lymphocytic leukemia and explore extended versus standard-length ofatumumab treatment. Patients (79 ofatumumab, 43 physicians' choice) completed a median 6 (ofatumumab) or 3 (physicians' choice) months' therapy. Ofatumumab-treated patients with stable disease or better were randomized (2:1) to 6 months' extended ofatumumab treatment or observation. Although the study did not meet the primary endpoint of progression-free survival (PFS) by independent review committee (ofatumumab: 5.4 months, physicians' choice: 3.6 months; p = 0.27), median PFS by investigators was significantly longer for ofatumumab versus physicians' choice (7.0 versus 4.5 months; p = 0.003) as was time to next therapy (median 11.5 versus 6.5 months; p = 0.0004). PFS and time to next therapy were significantly longer with ofatumumab extended treatment than observation (p = 0.026 and p = 0.002, respectively; n = 37). The adverse-event profile of long-term ofatumumab administration showed no unexpected findings (Clinicaltrials.gov identifier: NCT01313689).
authors.affiliation: a Department of Hematology , Karolinska University Hospital , Stockholm , Sweden ;
authors.forename: Anders
authors.initials: A
authors.lastname: Österborg
authors.affiliation: b Institute of Internal Medicine Building B, Haemopoetic Transplantation Centre, DEOEC (Debreceni Egyetem Orvos És Egészségtudományi Centrum) , Debrecen , Hungary ;
authors.forename: Miklós
authors.initials: M
authors.lastname: Udvardy
authors.affiliation: c Center of Heart Blood and Endocrinology , St Petersburg , Russia ;
authors.forename: Andrey
authors.initials: A
authors.lastname: Zaritskey
authors.affiliation: d Södra Älvsborgs Sjukhus , Borås , Sweden ;
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Andersson
authors.affiliation: e Department of Cancer Prevention , Faculty of Public Health, Silesian Medical University , Katowice , Poland ;
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grosicki
authors.affiliation: f Wroclaw Medical University , Wroclaw , Poland ;
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Mazur
authors.affiliation: g Dnipropetrovsk City Clinical Hospital No. 4 , Dnipropetrovsk , Ukraine ;
authors.forename: Polina
authors.initials: P
authors.lastname: Kaplan
authors.affiliation: h Innsbruck Medical University , Innsbruck , Austria ;
authors.forename: Michael
authors.initials: M
authors.lastname: Steurer
authors.affiliation: i Churchill Hospital , Oxford , UK ;
authors.forename: Anna
authors.initials: A
authors.lastname: Schuh
authors.affiliation: j Ospedale Niguarda Ca'Granda , Milan , Italy ;
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.affiliation: k National Cancer Institute , Kiev , Ukraine ;
authors.forename: Iryna
authors.initials: I
authors.lastname: Kryachok
authors.affiliation: l Universitaetsklinikum Carl Gustav Carus , Dresden , Germany ;
authors.forename: Jan Moritz
authors.initials: JM
authors.lastname: Middeke
authors.affiliation: m Makiivka City Hospital #2 of Donetsk Region , Makiivka , Ukraine ;
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Kulyaba
authors.affiliation: n Khmelnytskyi Regional Hospital , Khmelnytskyi , Ukraine ;
authors.forename: Grygoriy
authors.initials: G
authors.lastname: Rekhtman
authors.affiliation: o Pfizer Inc , Collegeville , PA , USA ;
authors.forename: Michele
authors.initials: M
authors.lastname: Gorczyca
authors.affiliation: p Novartis Pharmaceuticals , Dublin , Ireland ;
authors.forename: Siobhan
authors.initials: S
authors.lastname: Daly
authors.affiliation: q Novartis Pharmaceuticals, Research Triangle Park , NC , USA ;
authors.forename: Chai-Ni
authors.initials: CN
authors.lastname: Chang
authors.affiliation: r Genmab , Copenhagen , Denmark ;
authors.forename: Steen
authors.initials: S
authors.lastname: Lisby
authors.affiliation: s Novartis Pharmaceuticals , Wayne , PA , USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Gupta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014740:Vidarabine; C527517:ofatumumab; C024352:fludarabine
keywords: Anti-CD20 monoclonal antibody; chronic lymphocytic leukemia; extended-length therapy; ofatumumab; phase III clinical trial