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  • Original Article
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Multiple Myeloma, Gammopathies

A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma

Leukemia volume 30, pages 1320–1326 (2016)Cite this article

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Abstract

This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ⩾75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ⩾3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ⩾3 AEs included infections (8–20%), and constitutional (10–14%) and cardiovascular events (4–12%); peripheral neuropathy was limited (4–6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.

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Acknowledgements

We thank all the patients who participated in the study, the nurses Rosalia Capobianco and Giacomo Castorina, the data managers Giulia Lupparelli, Marta Santoro and the editorial assistant Giorgio Schirripa.

Author contributions

AL, MB, PS, and AP designed the study and supervised its conduct and the data analysis. AL, SB, MTP, SO, APF, TC, OV, GB, AML, FM, VM, RP, LDR, PO, IDV, SS, AMC, EP, DD, MG, TG, CN, EA, LDP, CC, CM and MO recruited patients in the source studies and/or provided relevant data. AL collected and assembled the data. RP and SS performed the statistical analysis. AL and AP analyzed and interpreted the data. AL and AP drafted the initial manuscript. All authors were given unrestricted access to the data, critically reviewed the manuscript drafts, approved the final version and made the decision to submit it for publication.

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Authors and Affiliations

  1. Division of Hematology, Myeloma Unit, University of Torino, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Torino, Italy

    A Larocca, S Bringhen, S Oliva, P Omedé, S Spada, E Ponticelli, M Genuardi, E Aghemo, M Boccadoro & A Palumbo

  2. Division of Hematology, Department of Cellular Biotechnologies and Hematology, 'Sapienza' University, Rome, Italy

    M T Petrucci

  3. IRCCS Casa Sollievo della Sofferenza, Unità di Ematologia, San Giovanni Rotondo, Italy

    A P Falcone

  4. UOC Ematologia, Ospedale S Eugenio, Roma, Italy

    T Caravita

  5. Unit of Hematology and Stem Cell Transplantation, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (Pz), Italy

    O Villani

  6. Dipartimento di Ematologia ed Oncologia, SC Ematologia, AO Città della Salute e della Scienza di Torino, Torino, Italy

    G Benevolo

  7. AO S Maria di Terni, SC Oncoematologia, Terni, Italy

    A M Liberati

  8. UOC di Ematologia AO Cosenza, Cosenza, Italy

    F Morabito

  9. Department of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    V Montefusco

  10. Division of Nuclear Medicine, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy

    R Passera

  11. Hematology and SCT Unit, Osp SCamillo, Rome, Italy

    L De Rosa

  12. Divisione di Ematologia, Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy

    I D Vincelli

  13. IRCCS AOU San Martino-IST, Genova, Italy

    A M Carella

  14. UO Ematologia e Centro Trapianti, Ospedale Oncologico di Riferimento Regionale 'Armando Businco', Cagliari, Italy

    D Derudas

  15. Divisione di Medicina Interna ed Ematologia, AUO San Luigi Gonzaga, Orbassano, Italy

    T Guglielmelli

  16. SODc Ematologia, AOU Careggi, Florence, Italy

    C Nozzoli

  17. Division of Hematology, Department of Translational Medicine Amedeo Avogadro University, Ospedale Maggiore della Carità, Novara, Italy

    L De Paoli

  18. Division of Hematology, Azienda Policlinico-OVE, University of Catania, Catania, Italy

    C Conticello

  19. UOC Ematologia, Azienda Ospedaliera Universitaria, G Martino, Messina, Italy

    C Musolino

  20. Clinica di Ematologia AOU Ospedali Riuniti di Ancona, Ancona, Italy

    M Offidani

  21. Department of Hematology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands

    P Sonneveld

Authors
  1. A Larocca
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  2. S Bringhen
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  7. O Villani
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  9. A M Liberati
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  12. R Passera
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  13. L De Rosa
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  14. P Omedé
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  15. I D Vincelli
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  16. S Spada
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  17. A M Carella
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  18. E Ponticelli
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  19. D Derudas
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  20. M Genuardi
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  21. T Guglielmelli
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  22. C Nozzoli
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  23. E Aghemo
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  24. L De Paoli
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  25. C Conticello
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  26. C Musolino
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  27. M Offidani
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  28. M Boccadoro
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  29. P Sonneveld
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  30. A Palumbo
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Corresponding author

Correspondence to A Palumbo.

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Competing interests

AL has received honoraria from Celgene and Jannsen-Cilag. SB has received honoraria from Celgene, Janssen-Cilag and served on the advisory committee for Mundipharma. MTP has received honoraria from Celgene, Janssen-Cilag, Mundipharma, Sanofi, Amgen and Bristol-Myers Squibb. TC has received honoraria from Celgene, J&J, Amgen and Bristol-Myers Squibb. TG has received research funding from Celgene. CN has received honoraria from Celgene, Janssen-Cilag and Mundipharma. MO has received honoraria from Janssen-Cilag. MB has received consultancy fees from and served on the scientific advisory board for Jannsen-Cilag, Sanofi, Amgen and Celgene. PS has received research support from Onyx, Janssen, Celgene, Millennium and served on the advisory board for Onyx, Janssen, Celgene and Millennium. AP has received consultancy fees, research funding and honoraria from Jannsen-Cilag.

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Larocca, A., Bringhen, S., Petrucci, M. et al. A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma. Leukemia 30, 1320–1326 (2016). https://doi.org/10.1038/leu.2016.36

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