title: Ofatumumab retreatment and maintenance in fludarabine-refractory chronic lymphocytic leukaemia patients.
abstract: There are limited data on retreatment with monoclonal antibodies (mAb) in patients with chronic lymphocytic leukaemia (CLL). In a pivotal study, ofatumumab (human anti-CD20 mAb) monotherapy demonstrated a 47% objective response rate (ORR) in fludarabine refractory CLL patients. From this study, a subset of 29 patients who had at least stable disease and then progressed were retreated with eight weekly ofatumumab infusions (induction treatment period), followed by monthly infusions for up to 2 years (maintenance treatment period). The ORR after 8 weeks of induction retreatment was 45% and 24% had continued disease control after maintenance at 52 weeks. Efficacy and safety of the retreated patients were compared with their initial results in the pivotal study. Response duration was 24.1 months vs. 6.8 months; time to next therapy was 14.8 months vs. 12.3 months; and progression-free survival was 7.4 months vs. 7.9 months (medians). Upon retreatment, 72% had infusion reactions, mostly Grade 1-2. Three patients had fatal infections. In summary, ofatumumab retreatment and maintenance therapy was feasible in patients with heavily pretreated CLL and appeared to result in more durable disease control than initial ofatumumab treatment in this subset of patients who may have a more favourable disease profile.
authors.affiliation: Department of Haematology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Österborg
authors.affiliation: The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.|Cancer Therapy Research Center, San Antonio, TX, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.affiliation: Department of Internal Medicine/Haemato-Oncology, Faculty Hospital Brno, Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Mayer
authors.affiliation: Johannes-Gutenberg-Universtitaer Mainz, Mainz, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
authors.affiliation: Leeds Teaching Hospital, Leeds, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.affiliation: Univesitatetsklinickum Carl Gustav Carus, Dresden, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.affiliation: Churchill Hospital, Oxford, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Schuh
authors.affiliation: Faculty of Medicine in Hradec Kralove, University Hospital and Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Smolej
authors.affiliation: Haematologisch-Onkologisches Institut, Moenchengladbach-Rheydt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Beck
authors.affiliation: Hopital Jean Bernanrd, Poitiers, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreyfus
authors.affiliation: Akademia Medyczna w Gdansku, Gdansk, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellman
authors.affiliation: Universitetssjukhuset, Orebro, Sweden.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kozlowski
authors.affiliation: Universitaesklinikum des Saarlandes, Homburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.affiliation: Azienda Ospendaliero Universitaria Policlinico Consorziale, Bari, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rizzi
authors.affiliation: Fakultni nemocnice, Praha10, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Spacek
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Phillips
authors.affiliation: GlaxoSmithKline, Collegeville, PA, USA.
authors.forename: Ira V
authors.initials: IV
authors.lastname: Gupta
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Williams
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Roxanne C
authors.initials: RC
authors.lastname: Jewell
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Noelia
authors.initials: N
authors.lastname: Nebot
authors.affiliation: Genmab, AS, Copenhagen, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Lisby
authors.affiliation: Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, UK.
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D019233:Retreatment; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014740:Vidarabine; C527517:ofatumumab; C024352:fludarabine
keywords: anti-CD20 monoclonal antibody; chronic lymphocytic leukaemia; maintenance; ofatumumab; retreatment