title: Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia.
abstract: We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. Total number of patients was 103; median age was 65 years (range 39-85). Median number of prior lines of therapy was 4 (range 1-13), including, in most cases, rituximab-, fludarabine- and alemtuzumab-based regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3-4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. This study is registered at clinicaltrials.gov identifier:01453062.
authors.affiliation: Hematology, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Niguarda Ca' Granda Hospital, Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.affiliation: 1 Department of Internal Medicine, University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Panayiotidis
authors.affiliation: 1 Department of Internal Medicine, University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Dimou
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Bloor
authors.affiliation: Hôpitaux Universitaire Henri Mondor, Créteil, France.
authors.forename: Jehan
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Churchill Hospital, Oxford, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Schuh
authors.affiliation: Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Norin
authors.affiliation: Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Geisler
authors.affiliation: St. James's University Hospital, Leeds, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.affiliation: Department of Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Doubek
authors.affiliation: Charles University Hospital, Praha, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Trněný
authors.affiliation: Charles University Hospital, Praha, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Obrtlikova
authors.affiliation: Catholic University Sacred Heart, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.affiliation: Department of Internal Medicine III, Ulm University, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.affiliation: University Hospital Hradec Kralove, Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Smolej
authors.affiliation: Department of Onco-Hematology, University Vita-Salute San Raffaele and Scientific Institut San Raffaele, Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.affiliation: Hôpital Avicenne, Bobigny, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Cymbalista
authors.affiliation: Hematology, Medical University of Vienna, Austria.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
authors.affiliation: G. Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.affiliation: G. Papanicolaou Hospital, Thessaloniki, Greece.
authors.forename: Niki
authors.initials: N
authors.lastname: Stavroyianni
authors.affiliation: Hematology, Trafford General Hospital, Manchester, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Carrington
authors.affiliation: Groupe Hospitalier Pitié Salpêtrière, Paris, France.
authors.forename: Hamadi
authors.initials: H
authors.lastname: Zouabi
authors.affiliation: Groupe Hospitalier Pitié Salpêtrière, Paris, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Leblond
authors.affiliation: Hospital General de Albacete, Albacete, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Gomez-Garcia
authors.affiliation: Hospital General de Albacete, Albacete, Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Rubio
authors.affiliation: Policlinico di Modena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.affiliation: IRST Meldola, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Musuraca
authors.affiliation: Azienda Ospedaliero Universitaria Careggi, Firenze, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Rigacci
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Farina
authors.affiliation: ULSS 18-Rovigo Ospedale "S.Maria della Misericordia', Rovigo, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Paolini
authors.affiliation: Department of Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
authors.affiliation: Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.affiliation: dACRO Research & Education Group, University of Glasgow, UK.
authors.forename: Colm
authors.initials: C
authors.lastname: Bradley
authors.affiliation: Hematology, Hospital Clínic, Barcelona, Spain emontse@clinic.ub.es.
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
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; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; 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; D012074:Remission Induction; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C527517:ofatumumab