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Chronic lymphocytic leukemia

Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial

Leukemia volume 31, pages 1922–1927 (2017)Cite this article

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Abstract

The phase III trial GEM05MENOS65 randomized 390 patients 65 years old or younger with newly diagnosed symptomatic multiple myeloma (MM) to receive induction with thalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone and Vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone bortezomib (VBMCP/VBAD/B) followed by autologous stem cell transplantation (ASCT) with MEL-200. After ASCT, a second randomization was performed to compare thalidomide/bortezomib (TV), thalidomide (T) and alfa-2b interferon (alfa2-IFN). Maintenance treatment consisted of TV (thalidomide 100 mg daily plus one cycle of intravenous bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 every 3 months) versus T (100 mg daily) versus alfa2-IFN (3 MU three times per week) for up to 3 years. A total of 271 patients were randomized (TV: 91; T: 88; alfa2-IFN: 92). The complete response (CR) rate with maintenance was improved by 21% with TV, 11% with T and 17% with alfa2-IFN (P, not significant). After a median follow-up of 58.6 months, the progression-free survival (PFS) was significantly longer with TV compared with T and alfa2-IFN (50.6 vs 40.3 vs 32.5 months, P=0.03). Overall survival was not significantly different among the three arms. Grade 2–3 peripheral neuropathy was observed in 48.8%, 34.4% and 1% of patients treated with TV, T and alfa2-IFN, respectively. In conclusion, bortezomib and thalidomide maintenance resulted in a significantly longer PFS when compared with thalidomide or alfa2-IFN. (no. EUDRA 2005-001110-41).

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Acknowledgements

This work has been supported in part by grants RD12/0036/0046 and PI12/1093 from Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER), and 2014SGR-552 from AGAUR (Generalitat de Catalunya).

Author contributions

JB, LR, JJL and JSM designed the trial; all authors performed the research; AO performed the statistical analysis; LR and JB analyzed and interpreted the data; LR wrote the initial draft of the manuscript; JB, AO, MVM, JJL and JSM reviewed the draft manuscript; and all authors approved the final version for submission.

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Authors and Affiliations

  1. Department of Hematology, Hospital Clínic de Barcelona, Barcelona, Spain

    L Rosiñol, MaT Cibeira & J Bladé

  2. Department of Hematology, Hospital Germans Trias I Pujol, Badalona, Spain

    A Oriol

  3. Department of Hematology, Hospital Clínico Universitario de Valencia, Valencia, Spain

    A I Teruel

  4. Department of Hematology, Hospital Universitario La Paz, Madrid, Spain

    A L de la Guía

  5. Department of Hematology, Hospital Ramón y Cajal, Madrid, Spain

    MaJ Blanchard

  6. Department of Hematology, Hospital La Fe, Valencia, Spain

    J de la Rubia

  7. Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    M Granell

  8. Department of Hematology, Complejo Asistencial Son Espases, Palma de Mallorca, Spain

    MaA Sampol

  9. Department of Hematology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain

    L Palomera

  10. Department of Hematology, Hospital Universitari Josep Trueta, Girona, Spain

    Y González

  11. Department of Hematology, Hospital de Donostia, Donostia, Spain

    MaA Etxebeste

  12. Department of Hematology, Hospital Clínico Universitario San Carlos, Madrid, Spain

    R Martínez-Martínez

  13. Department of Hematology, Hospital Universitario de Canarias, La Laguna, Spain

    M T Hernández

  14. Department of Hematology, Hospital Morales Messeguer, Murcia, Spain

    F de Arriba

  15. Department of Hematology, Hospital La Princesa, Madrid, Spain

    A Alegre

  16. Department of Hematology, Hospital Clínico Universitario de Salamanca, Salamanca, Spain

    MaV Mateos

  17. Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain

    J Martínez-López & J J Lahuerta

  18. Department of Hematology, Clínica Universitaria de Navarra, Pamplona, Spain

    J San Miguel

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  1. L Rosiñol
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on behalf of the Programa Español de Tratamientos en Hematología/Grupo Español de Mieloma (PETHEMA/GEM)

Corresponding author

Correspondence to J Bladé.

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Competing interests

LR received honoraria from Janssen and Celgene, AO has served as member of advisory boards for Janssen and Celgene, MVM has served as member of advisory boards for Celgene, Janssen and Millenium, JJL received honoraria from Janssen and Celgene, JSM discloses consultation fees from Celgene, Janssen and Millenium, and JB received grant support from Janssen and received honoraria from Janssen and Celgene. The remaining authors declare no conflict of interest.

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Rosiñol, L., Oriol, A., Teruel, A. et al. Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial. Leukemia 31, 1922–1927 (2017). https://doi.org/10.1038/leu.2017.35

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