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

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. BroijlH. 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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
DOIs	https://doi.org/10.1038/leu.2017.211
Publication status	Published - 1 Feb 2018

Keywords

STEM-CELL TRANSPLANTATION
DIAGNOSED MULTIPLE-MYELOMA
2ND PRIMARY MALIGNANCIES
RANDOMIZED-TRIAL
DEXAMETHASONE COMBINATION
INTERGROUPE FRANCOPHONE
MAINTENANCE TREATMENT
PLUS DEXAMETHASONE
STAGING SYSTEM
DELETION 17P

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10.1038/leu.2017.211

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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. Leukemia, 32(2), 383-390. https://doi.org/10.1038/leu.2017.211

@article{6141464858884285aa587acffccd2580,

title = "Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 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 = "STEM-CELL TRANSPLANTATION, DIAGNOSED MULTIPLE-MYELOMA, 2ND PRIMARY MALIGNANCIES, RANDOMIZED-TRIAL, DEXAMETHASONE COMBINATION, INTERGROUPE FRANCOPHONE, MAINTENANCE TREATMENT, PLUS DEXAMETHASONE, STAGING SYSTEM, DELETION 17P",

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 Kooy, {M. van Marwijk} 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,

day = "1",

doi = "10.1038/leu.2017.211",

language = "English",

volume = "32",

pages = "383--390",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Nature Publishing Group",

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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, Kooy, MVM, 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', 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

T2 - long-term results from the phase III HOVON-65/GMMGHD-4 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 - Kooy, M. van Marwijk

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 - 2018/2/1

Y1 - 2018/2/1

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 - STEM-CELL TRANSPLANTATION

KW - DIAGNOSED MULTIPLE-MYELOMA

KW - 2ND PRIMARY MALIGNANCIES

KW - RANDOMIZED-TRIAL

KW - DEXAMETHASONE COMBINATION

KW - INTERGROUPE FRANCOPHONE

KW - MAINTENANCE TREATMENT

KW - PLUS DEXAMETHASONE

KW - STAGING SYSTEM

KW - DELETION 17P

U2 - 10.1038/leu.2017.211

DO - 10.1038/leu.2017.211

M3 - Article

SN - 0887-6924

VL - 32

SP - 383

EP - 390

JO - Leukemia

JF - Leukemia

IS - 2

ER -