Bendamustine in combination with ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial.
We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m(2)) for 2 consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade ≥3 neutropenia was observed in 61.7% of patients; however, grade ≥3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features.
Hematology Unit, IRCCS Ca'Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Cortelezzi
Hematology Unit, IRCCS Ca'Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Sciumè
Department of Oncohematology, University of Perugia, Santa Maria Hospital, Terni, Italy.
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Liberati
Hematology Unit, IRCCS Ca'Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Vincenti
Department of Biomedical Sciences, Institute of Hematology, Azienda Ospedaliero-Universitaria Sant' Anna, Ferrara, Italy.
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Cuneo
Hematology Unit, IRCCS Ca'Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Reda
Department of Hematology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli, Rome, Italy.
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Laurenti
Clinic of Hematology DISM, Azienda Ospedaliera Universitaria S. Maria Misericordia, Piazzale Santa Maria della Misericordia, Udine, Italy.
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Zaja
Division of Hematology, Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy.
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Marasca
Department of Clinical and Molecular Biomedicine, Ferrarotto Hospital, University of Catania, Catania, Italy.
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Chiarenza
Hematology Unit, Ospedali Riuniti, Piazza Oms, Bergamo, Italy.
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Gritti
Division of Hematology II, San Giovanni Battista Hospital, Torino, Italy.
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Orsucci
Hematology Oncology Unit, Università Cattolica Sacro Cuore, Contrada Tappino, Campobasso, Italy.
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Storti
Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale Armando Businco, Cagliari, Italy.
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Angelucci
Hematology Unit, IRCCS 'Casa Sollievo della Sofferenza', Viale Cappuccini, San Giovanni Rotondo, Italy.
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Cascavilla
Division of Hematology, Department of Hemato-Oncology, S. Martino Hospital, University of Genova, Genova, Italy.
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Gobbi
Division of Hematology, Department of Cellular Biotechnologies and Hematology, 'Sapienza' University, Rome, Italy.
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Mauro
Hematology Unit, Cosenza Hospital Center, Cosenza, Italy.
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Morabito
Hematology Unit, IRCCS Ca'Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Fabris
GIMEMA Data Center, Rome, Italy.
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Piciocchi
Division of Hematology, Department of Cellular Biotechnologies and Hematology, 'Sapienza' University, Rome, Italy.
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Vignetti
Hematology Unit, IRCCS Ca'Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
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Neri
Division of Hematology, Department of Translational Medicine, A. Avogadro University of Eastern Piedmont, Novara, Italy.
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Rossi
Biostatistics Unit, Regina Elena Institute for Cancer Research and Treatment, Rome, Italy.
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Giannarelli
Division of Hematology, Department of Cellular Biotechnologies and Hematology, 'Sapienza' University, Rome, Italy.
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Guarini
Division of Hematology, Department of Cellular Biotechnologies and Hematology, 'Sapienza' University, Rome, Italy.
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Foà
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D012008:Recurrence
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride; C527517:ofatumumab