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Efficacy of bortezomib to intensify the conditioning regimen and the graft-versus-host disease prophylaxis for high-risk myeloma patients undergoing transplantation

Bone Marrow Transplantation volume 55, pages 419–430 (2020)Cite this article

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Abstract

This multicenter phase I trial was designed to evaluate the safety and efficacy of bortezomib (Bz) as part of both the conditioning regimen and the graft-versus-host disease (GvHD) prophylaxis. Patients received fludarabine, melphalan and Bz (days −9 and −2). GVHD prophylaxis consisted of Bz (days +1, +4, and +7), sirolimus (Siro) from day −5 and tacrolimus (Tk) from −3 (except the first five patients that did not receive Tk). Twenty-five patients with poor prognostic multiple myeloma were included. Eleven out of the 19 patients had high-risk features. Out of the 21 patients evaluable at day +100, 14 were in CR (67%) and 7 (33%) in PR. Cumulative incidence (CI) of nonrelapse mortality at 1 year was 24%. CI of grades 2–4 and 3–4 acute GvHD was 35% and 10%, respectively; CI of chronic GvHD was 35% and 55% at 1 and 2 years, respectively. Overall and event free survival at 2 years were 64% and 31%, respectively. Bz as part of the conditioning regimen and in the combination with Siro/tacrolimus for GvHD prophylaxis is safe and effective allowing an optimal disease control early after transplant and reducing the risk of GvHD.

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Acknowledgements

The authors would like to thank all patients and their families, physicians, research nurses, study coordinators, and research staff participating in this study. This trial was supported by Janssen and Celgene and the Ministerio de Sanidad y Política Social, convocatoria de concesión de ayudas para el fomento de la investigación clínica independiente 2010 (EC10–289); this study was partially supported by two grants from the Ministry of Health CIBER ONC, code CB16/12/00480. TCV was supported by a grant from Ministerio de Sanidad y Política Social (CM10/00161).

Authors contributions

Study design: TCV, LLC, CMRF, JSM, JPS. Patient enrollment: LLC, JM, EPL, DCB, MVM, JPS. Data collection: CCC, LLC, EPL, JM, CMRF. Biological studies: TCV, NP, CGC. Biological analysis: TCV, NP, CGC. Data analysis. TCV, FMM, JM, JPS. Data interpretation: TCV, CCC, LLC, JSM, JPS. Wrote or contributed to the writing of the paper: all authors.

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Authors and Affiliations

  1. Department of Hematology, University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CSIC/CIBERONC), Universidad de Sevilla, Seville, Spain

    T. Caballero-Velázquez, C. Calderón-Cabrera, F. Marquez-Malaver, C. García-Calderón, C. M. Rosso-Fernández, J. Martín & J. A. Pérez-Simón

  2. Department of Hematology, Complejo Asistencial Universitario de Salamanca-IBSAL-CIBERONC, Centro de Investigación del Cáncer-IBMCC, Salamanca, Spain

    L. López-Corral, N. Puig, E. Pérez-López, D. Caballero Barrigón & M. V. Mateos

  3. Clínica Universidad de Navarra, Centro Investigación Médica Aplicada (CIMA), IDISNA, CIBERONC, Pamplona, Spain

    J. San Miguel

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  1. T. Caballero-Velázquez
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on behalf of the European Myeloma Network

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Correspondence to J. A. Pérez-Simón.

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Conflict of interest

This trial was supported by Janssen and Celgene. TCV has received honoraria derived from lectures from Janssen and Celgene. JM has receive accommodation and registration fee for Reunión Anual Pethema 2016 from Janssen. MVM has received honoraria derived from lectures from Janssen and Celgene and from participation in advisory boards for Janssen and Celgene. JSM reports advisory board from Janssen and Celgene. JAPS has received honoraria derived from lectures and/or participation in advisory boards for Celgene and Janssen.

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This study was conducted in collaboration with the Grupo Español de Trasplante Hematopoyético (GETH) and chronic malignancies working party (CMWP) for the European Bone Marrow Transplant Group (EBMT).

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Caballero-Velázquez, T., Calderón-Cabrera, C., López-Corral, L. et al. Efficacy of bortezomib to intensify the conditioning regimen and the graft-versus-host disease prophylaxis for high-risk myeloma patients undergoing transplantation. Bone Marrow Transplant 55, 419–430 (2020). https://doi.org/10.1038/s41409-019-0670-6

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