Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial: long-term results from the phase III HOVON-65/GMMG-HD4 trial

H. Goldschmidt; H. M. Lokhorst; E. K. Mai; B. van der Holt; I. W. Blau; S. Zweegman; K. C. Weisel; E. Vellenga; M. Pfreundschuh; M. J. Kersten; C. Scheid; S. Croockewit; R. Raymakers; D. Hose; A. Potamianou; A. Jauch; J. Hillengass; M. Stevens-Kroef; M. S. Raab; A. Broijl; H. W. Lindemann; G. M. J. Bos; P. Brossart; M. van Marwijk Kooy; P. Ypma; U. Duehrsen; R. M. Schaafsma; U. Bertsch; T. Hielscher; Le Jarari; H. J. Salwender; P. Sonneveld

doi:10.1038/leu.2017.211

Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial: long-term results from the phase III HOVON-65/GMMG-HD4 trial

H. Goldschmidt
, H. M. Lokhorst
, E. K. Mai
, B. van der Holt
, I. W. Blau
, S. Zweegman
, K. C. Weisel
, E. Vellenga
, M. Pfreundschuh
, M. J. Kersten
, C. Scheid
, S. Croockewit
, R. Raymakers
, D. Hose
, A. Potamianou
, A. Jauch
, J. Hillengass
, M. Stevens-Kroef
, M. S. Raab
, A. Broijl

H. W. Lindemann, G. M. J. Bos, P. Brossart, M. van Marwijk Kooy, P. Ypma, U. Duehrsen, R. M. Schaafsma, U. Bertsch, T. Hielscher, Le Jarari, H. J. Salwender, P. Sonneveld

National Center for Tumor Diseases (NCT), University Clinic Heidelberg, Heidelberg, Germany.
Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
HOVON Data Center, Department of Hematology, Erasmus MC Cancer Center, Rotterdam, The Netherlands.
Internal Medicine, Charité University Medicine Berlin, Berlin, Germany.
Department of Hematology, Oncology, Immunology, Rheumatology and Pulmonology, University Hospital of Tuebingen, Tuebingen, Germany.
Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, The Netherlands.
Department of Hematology and Oncology, University Clinic of Saarland, Homburg, Germany.
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands, Amsterdam, The Netherlands; Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany.
Deptartment of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
EMEA Medical, Janssen, Athens, Greece.
Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
Laboratorium Tumor Genetica, Radboud University Medical Centre, Nijmegen,The Netherlands.
Department of Hematology, Erasmus MC Cancer Institute, Rotterdam 3015CN, the Netherlands.
Klinik für Hämatologie/Onkologie, Kath. Krankenhaus Hagen gem. GmbH - St-Marien-Hospital, Hagen, Germany.
Internal Medicine III, Oncology, Hematology and Rheumatology, University Clinic Bonn, Bonn, Germany.
Department of Hematology, Isala Clinics, Zwolle, The Netherlands.
Department of Hematology, Haga Hospital, The Hague, The Netherlands.
Department of Hematology, University Hospital Essen, Essen, Germany.
Department of Hematology, Medisch Spectrum Twente, Enschede, The Netherlands.
Division of Biostatistics, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
HOVON Datacenter, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Department of Hematology and Oncology, Asklepios Hospital Hamburg Altona, Hamburg, Germany.

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Abstract

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR) = 0.76, 95% confidence interval (95% CI) of 0.65-0.89, P = 0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR = 0.89, 95% CI: 0.74-1.08, P = 0.24). The incidence of SPM were similar between the two arms (7% each, P = 0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size >= 10%) and renal impairment at baseline (serum creatinine > 2 mg dl(-1)) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR = 1.02, P = 0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM

Original language	English
Pages (from-to)	383-390
Number of pages	8
Journal	Leukemia
Volume	32
Issue number	2
Early online date	2017
DOIs	https://doi.org/10.1038/leu.2017.211
Publication status	Published - Feb 2018

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SDG 3 Good Health and Well-being

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Journal Article

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10.1038/leu.2017.211

Bortezomib-before-and-after-high-dose-therapy-in-myeloma-long-term-results-from-the-phase-iii-hovon-65gmmghd-4-trial.pdfFinal published version, 515 KBLicence: Taverne

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Goldschmidt, H., Lokhorst, H. M., Mai, E. K., van der Holt, B., Blau, I. W., Zweegman, S., Weisel, K. C., Vellenga, E., Pfreundschuh, M., Kersten, M. J., Scheid, C., Croockewit, S., Raymakers, R., Hose, D., Potamianou, A., Jauch, A., Hillengass, J., Stevens-Kroef, M., Raab, M. S., ... Sonneveld, P. (2018). Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia, 32(2), 383-390. https://doi.org/10.1038/leu.2017.211

@article{d37f0de2b98e4d89af1e8e893f61076b,

title = "Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial: long-term results from the phase III HOVON-65/GMMG-HD4 trial",

abstract = "The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR) = 0.76, 95\% confidence interval (95\% CI) of 0.65-0.89, P = 0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR = 0.89, 95\% CI: 0.74-1.08, P = 0.24). The incidence of SPM were similar between the two arms (7\% each, P = 0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size >= 10\%) and renal impairment at baseline (serum creatinine > 2 mg dl(-1)) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR = 1.02, P = 0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM",

keywords = "Journal Article",

author = "H. Goldschmidt and Lokhorst, \{H. M.\} and Mai, \{E. K.\} and \{van der Holt\}, B. and Blau, \{I. W.\} and S. Zweegman and Weisel, \{K. C.\} and E. Vellenga and M. Pfreundschuh and Kersten, \{M. J.\} and C. Scheid and S. Croockewit and R. Raymakers and D. Hose and A. Potamianou and A. Jauch and J. Hillengass and M. Stevens-Kroef and Raab, \{M. S.\} and A. Broijl and Lindemann, \{H. W.\} and Bos, \{G. M. J.\} and P. Brossart and \{van Marwijk Kooy\}, M. and P. Ypma and U. Duehrsen and Schaafsma, \{R. M.\} and U. Bertsch and T. Hielscher and Le Jarari and Salwender, \{H. J.\} and P. Sonneveld",

year = "2018",

month = feb,

doi = "10.1038/leu.2017.211",

language = "English",

volume = "32",

pages = "383--390",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

number = "2",

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Goldschmidt, H, Lokhorst, HM, Mai, EK, van der Holt, B, Blau, IW, Zweegman, S, Weisel, KC, Vellenga, E, Pfreundschuh, M, Kersten, MJ, Scheid, C, Croockewit, S, Raymakers, R, Hose, D, Potamianou, A, Jauch, A, Hillengass, J, Stevens-Kroef, M, Raab, MS, Broijl, A, Lindemann, HW, Bos, GMJ, Brossart, P, van Marwijk Kooy, M, Ypma, P, Duehrsen, U, Schaafsma, RM, Bertsch, U, Hielscher, T, Jarari, L, Salwender, HJ & Sonneveld, P 2018, 'Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial: long-term results from the phase III HOVON-65/GMMG-HD4 trial', Leukemia, vol. 32, no. 2, pp. 383-390. https://doi.org/10.1038/leu.2017.211

TY - JOUR

T1 - Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial

T2 - long-term results from the phase III HOVON-65/GMMG-HD4 trial

AU - Goldschmidt, H.

AU - Lokhorst, H. M.

AU - Mai, E. K.

AU - van der Holt, B.

AU - Blau, I. W.

AU - Zweegman, S.

AU - Weisel, K. C.

AU - Vellenga, E.

AU - Pfreundschuh, M.

AU - Kersten, M. J.

AU - Scheid, C.

AU - Croockewit, S.

AU - Raymakers, R.

AU - Hose, D.

AU - Potamianou, A.

AU - Jauch, A.

AU - Hillengass, J.

AU - Stevens-Kroef, M.

AU - Raab, M. S.

AU - Broijl, A.

AU - Lindemann, H. W.

AU - Bos, G. M. J.

AU - Brossart, P.

AU - van Marwijk Kooy, M.

AU - Ypma, P.

AU - Duehrsen, U.

AU - Schaafsma, R. M.

AU - Bertsch, U.

AU - Hielscher, T.

AU - Jarari, Le

AU - Salwender, H. J.

AU - Sonneveld, P.

PY - 2018/2

Y1 - 2018/2

N2 - The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR) = 0.76, 95% confidence interval (95% CI) of 0.65-0.89, P = 0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR = 0.89, 95% CI: 0.74-1.08, P = 0.24). The incidence of SPM were similar between the two arms (7% each, P = 0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size >= 10%) and renal impairment at baseline (serum creatinine > 2 mg dl(-1)) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR = 1.02, P = 0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM

AB - The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR) = 0.76, 95% confidence interval (95% CI) of 0.65-0.89, P = 0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR = 0.89, 95% CI: 0.74-1.08, P = 0.24). The incidence of SPM were similar between the two arms (7% each, P = 0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size >= 10%) and renal impairment at baseline (serum creatinine > 2 mg dl(-1)) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR = 1.02, P = 0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM

KW - Journal Article

U2 - 10.1038/leu.2017.211

DO - 10.1038/leu.2017.211

M3 - Article

C2 - 28761118

SN - 0887-6924

VL - 32

SP - 383

EP - 390

JO - Leukemia

JF - Leukemia

IS - 2

ER -

Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial: long-term results from the phase III HOVON-65/GMMG-HD4 trial

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