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Outcomes with two different schedules of bortezomib, melphalan, and prednisone (VMP) for previously untreated multiple myeloma: matched pair analysis using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials

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Abstract

Bortezomib–melphalan–prednisone (VMP) is a standard-of-care for previously untreated, transplant-ineligible multiple myeloma (MM). Here, we compared outcomes between VMP regimens in the VISTA trial (9-cycle VMP schedule, including 4 cycles of twice weekly bortezomib) and the PETHEMA/GEM05 trial (less intensive 6-cycle VMP schedule with 1 cycle of twice weekly and 5 cycles of weekly bortezomib, then bortezomib-based maintenance). A total of 113 patient pairs matched by propensity score (estimated using logistic regression and incorporating eight exposure/outcome-related parameters) were included in this retrospective analysis. Median cumulative bortezomib dose was higher in PETHEMA/GEM05 than VISTA (49.6 vs 37.0 mg/m2); median dose intensity was lower (2.0 vs 5.1 mg/m2/month). Median progression-free survival (PFS) and time-to-progression (TTP) were significantly longer in PETHEMA/GEM05 than VISTA (PFS, 30.5 vs 20.0 months, p = 0.0265; TTP, 33.8 vs 24.2 months, p = 0.0049) after a median follow-up of 77.2 and 26.0 months, respectively. Median overall survival (OS) was similar (61.3 vs 61.0 months, p = 0.6528; median follow-up, 77.6 vs 60.1 months). Post-induction complete response rate was lower in PETHEMA/GEM05 than VISTA (19 vs 31 %; p = 0.03318); on-study (including maintenance) rate was similar (30 vs 31 %; p = 0.89437). This analysis suggests that the less-intensive PETHEMA/GEM05 VMP regimen plus maintenance may improve PFS and TTP, but not OS, compared with the VISTA VMP regimen.

Trial registrations

NCT00111319, NCT00443235

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Acknowledgments

The authors would like to acknowledge the writing support of Catherine Crookes of FireKite, an Ashfield company, part of UDG Healthcare plc, and Mark Richardson, who provided medical writing support on behalf of FireKite, during the development of this manuscript, which was funded by Janssen Global Services, LLC.

Author contributions

M-VM and JSM designed the research study

M-VM, AO, JM-L, A-IT, EB, LuisP, FdA provided patients for the analysis

M-VM, JSM, HvdV, LixiaP, D-LE, AC developed the analytical plan and/or interpreted the data

M-VM co-wrote the paper; all authors contributed to the writing of the paper and approved the final version.

Author information

Authors and Affiliations

  1. Servicio de Hematología, Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Paseo San Vicente 58-182, Salamanca, 37007, Spain

    Maria-Victoria Mateos

  2. Clinical Hematology Service and Oncohematological Clinical Trial Unit of the Institut Català d’Oncologia (ICO), Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Barcelona, Spain

    Albert Oriol

  3. Hospital Universitario 12 de Octubre, S de Hematología HUNET-CRIS Unidad Ensayos Tempranos, Madrid, Spain

    Joaquín Martínez-López

  4. Hospital Clínico Universitario de Valencia, Servicio de Hematología, Valencia, Spain

    Ana-Isabel Teruel

  5. Hospital de Donostia, Servicio de Hematología, Paseo Dr. Beguiristain 115, 20014, Donostia - San Sebastian (Guipúzcoa), Spain

    Enrique Bengoechea

  6. Servicio de Hematología, Hospital Clínico Universitario “Lozano Blesa” Zaragoza, Instituto de Investigación Sanitaria (ISS) de Aragón, Zaragoza, Spain

    Luis Palomera

  7. Servicio de Hematología y Hemoterapia, Hospital General Universitario Morales Meseguer, Murcia, Spain

    Felipe de Arriba

  8. Oncology Clinical Research, Millennium Pharmaceuticals, Inc, Cambridge, MA, USA

    Dixie-Lee Esseltine & Helgi van de Velde

  9. Janssen Research & Development, High Wycombe, United Kingdom

    Andrew Cakana

  10. Janssen Research & Development, LLC, Raritan, NJ, USA

    Lixia Pei

  11. Department of Hematology, Clinica Universidad de Navarra-CIMA-IDSINA, Pamplona, Spain

    Jesus San Miguel

Authors
  1. Maria-Victoria Mateos
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  2. Albert Oriol
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  3. Joaquín Martínez-López
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  4. Ana-Isabel Teruel
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  5. Enrique Bengoechea
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  6. Luis Palomera
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  7. Felipe de Arriba
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  8. Dixie-Lee Esseltine
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  10. Lixia Pei
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  11. Helgi van de Velde
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  12. Jesus San Miguel
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Corresponding author

Correspondence to Maria-Victoria Mateos.

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Author disclosures

M-VM has received honoraria from Janssen, Millennium, and Celgene.

AO has been on Advisory Boards for and has received personal fees from Celgene and Janssen.

JM-L has received honoraria from Janssen and Celgene.

A-IT has nothing to disclose.

EB has nothing to disclose.

LuisP has nothing to disclose.

FdA has received honoraria from Janssen, Amgen, and Celgene.

D-LE is an employee of Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited and has stock or ownership interest in Johnson & Johnson and Takeda Pharmaceuticals Inc.

AC is an employee of Janssen Pharmaceutical and has stock or ownership interest in Johnson & Johnson.

LixiaP is an employee of Janssen R&D and has stock or ownership interest in Johnson & Johnson.

HVdV is an employee of Millennium Pharmaceuticals, Inc, Boston, MA, USA, formerly of Janssen, and has stock or other ownership interest in Johnson & Johnson.

JSM has had a consultant or advisory role for and has received honoraria from Janssen, Millennium, Celgene, Novartis, Bristol-Myers Squibb, MSD, and Onyx.

Research involving human participants and/or animals

For this type of study, formal consent is not required OR

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

This article does not contain any studies with animals performed by any of the authors.

Statement of prior presentation

Maria-Victoria Mateos, Albert Oriol, Joaquín Martínez-López et al. Matched pair analysis of outcomes with bortezomib, melphalan, and prednisone (VMP) treatment for previously untreated multiple myeloma (MM) using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials. Clin Lymphoma Myeloma Leuk 2015;15 (Suppl 3): e73 (abstract BP-048).

Funding

The VISTA trial was sponsored by Johnson & Johnson Pharmaceutical Research & Development and Millennium Pharmaceuticals, Inc. The PETHEMA/GEM05 study was funded and sponsored by PETHEMA (Spanish Program for the Treatment of Hematologic Diseases) and was coordinated by the Spanish Myeloma Group (PETHEMA/GEM05; Chair Joan Blade). Cytogenetic and minimal residual disease studies were supported by a grant from FIS (Fondo de Investigación Sanitaria) 06/1354. The manufacturers of bortezomib (Johnson & Johnson Pharmaceutical Research and Development) and thalidomide (Celgene Corporation, Summit) supplied both drugs free and provided grants to support the trial.

The present matched pair analysis was sponsored by Janssen Global Services, LLC.

Conflict of interest

The authors declare that they have no conflict of interest.

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Mateos, MV., Oriol, A., Martínez-López, J. et al. Outcomes with two different schedules of bortezomib, melphalan, and prednisone (VMP) for previously untreated multiple myeloma: matched pair analysis using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials. Ann Hematol 95, 2033–2041 (2016). https://doi.org/10.1007/s00277-016-2835-3

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