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Chronic Lymphocytic Leukemia

Bendamustine in combination with Ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial

Leukemia volume 28, pages 642–648 (2014)Cite this article

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Abstract

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/m2) 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.

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Acknowledgements

We thank the clinicians, nurses and data managers of the 14 institutions who entered their patients into the GIMEMA CLL0809 study and provided the necessary data to make this study possible. In addition, we are grateful to those who spent their time to quality-control tasks. Finally, the study could not have been a success without the continuous efforts of the members of the GIMEMA data center.

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Authors and Affiliations

  1. Hematology Unit, IRCCS Ca’Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

    A Cortelezzi, M Sciumè, D Vincenti, G Reda, S Fabris & A Neri

  2. Department of Oncohematology, University of Perugia, Santa Maria Hospital, Terni, Italy

    A M Liberati

  3. Department of Biomedical Sciences, Institute of Hematology, Azienda Ospedaliero-Universitaria Sant’ Anna, Ferrara, Italy

    A Cuneo

  4. Department of Hematology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli, Rome, Italy

    L Laurenti

  5. Clinic of Hematology DISM, Azienda Ospedaliera Universitaria S. Maria Misericordia, Piazzale Santa Maria della Misericordia, Udine, Italy

    F Zaja

  6. Division of Hematology, Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy

    R Marasca

  7. Department of Clinical and Molecular Biomedicine, Ferrarotto Hospital, University of Catania, Catania, Italy

    A Chiarenza

  8. Hematology Unit, Ospedali Riuniti, Piazza Oms, Bergamo, Italy

    G Gritti

  9. Division of Hematology II, San Giovanni Battista Hospital, Torino, Italy

    L Orsucci

  10. Hematology Oncology Unit, Università Cattolica Sacro Cuore, Contrada Tappino, Campobasso, Italy

    S Storti

  11. Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale Armando Businco, Cagliari, Italy

    E Angelucci

  12. Hematology Unit, IRCCS ‘Casa Sollievo della Sofferenza’, Viale Cappuccini, San Giovanni Rotondo, Italy

    N Cascavilla

  13. Division of Hematology, Department of Hemato-Oncology, S. Martino Hospital, University of Genova, Genova, Italy

    M Gobbi

  14. Division of Hematology, Department of Cellular Biotechnologies and Hematology, ‘Sapienza’ University, Rome, Italy

    F R Mauro, M Vignetti, A Guarini & R Foà

  15. Hematology Unit, Cosenza Hospital Center, Cosenza, Italy

    F Morabito

  16. GIMEMA Data Center, Rome, Italy

    A Piciocchi

  17. Division of Hematology, Department of Translational Medicine, A. Avogadro University of Eastern Piedmont, Novara, Italy

    D Rossi

  18. Biostatistics Unit, Regina Elena Institute for Cancer Research and Treatment, Rome, Italy

    D Giannarelli

Authors
  1. A Cortelezzi
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  2. M Sciumè
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  3. A M Liberati
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  4. D Vincenti
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  5. A Cuneo
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  6. G Reda
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  7. L Laurenti
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  8. F Zaja
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  9. R Marasca
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  10. A Chiarenza
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  11. G Gritti
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  12. L Orsucci
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  13. S Storti
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  14. E Angelucci
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  15. N Cascavilla
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  16. M Gobbi
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  17. F R Mauro
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  18. F Morabito
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  19. S Fabris
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  20. A Piciocchi
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  21. M Vignetti
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  22. A Neri
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  23. D Rossi
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  24. D Giannarelli
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  25. A Guarini
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  26. R Foà
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Consortia

on behalf of the GIMEMA Chronic Lymphoproliferative Disorders Working Party

Corresponding author

Correspondence to A Cortelezzi.

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Competing interests

FZ received compensation as a member of advisory board of Roche, GlaxoSmithKline, Mundipharma and AMGEN Biotech. FM received honoraria from Mundipharma and GlaxoSmithKline. MG received compensation as a member of the advisory board by Mundipharma and GlaxoSmithKline. DR received honoraria from GlaxoSmithKline. RF received compensation by GlaxoSmithKline and Mundipharma as expert testimony. The remaining authors declare no conflict of interest.

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Cortelezzi, A., Sciumè, M., Liberati, A. et al. Bendamustine in combination with Ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial. Leukemia 28, 642–648 (2014). https://doi.org/10.1038/leu.2013.334

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