Bortezomib Induction and Maintenance Treatment Improves Survival In Patients With Newly Diagnosed Multiple Myeloma:Extended Follow-Up Of The HOVON-65/GMMG-HD4 Trial

Christof Scheid, Bronno van der Holt, Laila el Jarari, Uta Bertsch, Hans Salwender, Sonja Zweegman, Edo Vellenga, Annemiek Broyl, Igor Wolfgang Blau, Katja Weisel, Shulamit Wittebol, Gerard M.J. Bos, Marjan Stevens, Ingo GH Schmidt-Wolf, Michael Pfreundschuh, Dirk Hose, Anna Jauch, Helgi van de Velde, Reinier Raymakers, Martyn Ronald Schaafsma & 7 others Marie Jose Kersten, Marinus van Marwijk Kooy, Ulrich Duehrsen, Hans Walter Lindemann, Pierre W. Wijermans, Henk Lokhorst, H. Goldschmidt

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background We investigated if bortezomib during induction and maintenance improves survival in newly diagnosed Multiple Myeloma (MM).\r\n\r\nMethods 827 eligible patients with newly diagnosed symptomatic MM were randomized to receive induction therapy with VAD (vincristine, doxorubicin, dexamethasone; n=414) or PAD (bortezomib, doxorubicin, dexamethasone; n=413) followed by high-dose melphalan (HDM) and autologous stem cell transplant (ASCT). Maintenance consisted of daily thalidomide 50 mg (VAD) or 2-weekly bortezomib 1.3 mg/m2 i.v. (PAD) for 2 years. The primary analysis was progression-free survival (PFS) adjusted for ISS stage. We here report long-term results of this trial ( P. Sonneveld et al., J Clin Oncol 2012;30:2946-2955 ).\r\n\r\nResults The number of eligible patients, patient characteristics and disease characteristics are similar to those reported before. The response rates during protocol treatment have improved slightly since all patients have now completed treatment: CR+nCR 49% vs 35%, VGPR 26% vs 21% and ≥PR 91% vs 83% (PAD vs VAD).\r\n\r\nAfter a median follow-up of 67 months, 111 of patients treated with VAD and 131 of patients treated with PAD were progression-free and alive. Progression-free survival (PFS) defined as time from randomization until progression, relapse or death (censored at date of alloSCT, if applicable), was superior with PAD when adjusted for ISS, (HR=0.78, 95% CI [0.66-0.91], P=.002) and in multivariate analysis (HR=0.76 (95% CI [0.64-0.90], P=.001). For the secondary endpoint overall survival (OS) the PAD arm was superior when adjusted for ISS (HR=0.80, 95% CI [0.65-1.00], P=.047) as well as in multivariate analysis (HR=0.78, 95% CI [0.63-0.97], P=.027). Landmark analysis from start of maintenance for PFS did not show a significant difference between Thalidomide and Bortezomib maintenance, however, for OS the PAD arm was superior (P=.035) (HR=0.71, 95% CI [0.52-0.98]). Subgroup analysis performed on patients with renal failure at presentation (serum creatinine ≥2 mg/dL; 45 VAD, 36 PAD) showed that the PAD arm was significantly superior for PFS (HR=0.44, 95% CI [0.26-0.75], P=.003) and OS (HR=0.38, 95% CI [0.21-0.69], P
Original languageEnglish
Pages (from-to)404-404
Number of pages1
JournalBlood
Volume122
Issue number21
Publication statusPublished - 2013

Cite this

Scheid, Christof ; Holt, Bronno van der ; Jarari, Laila el ; Bertsch, Uta ; Salwender, Hans ; Zweegman, Sonja ; Vellenga, Edo ; Broyl, Annemiek ; Blau, Igor Wolfgang ; Weisel, Katja ; Wittebol, Shulamit ; Bos, Gerard M.J. ; Stevens, Marjan ; Schmidt-Wolf, Ingo GH ; Pfreundschuh, Michael ; Hose, Dirk ; Jauch, Anna ; Velde, Helgi van de ; Raymakers, Reinier ; Schaafsma, Martyn Ronald ; Kersten, Marie Jose ; Kooy, Marinus van Marwijk ; Duehrsen, Ulrich ; Lindemann, Hans Walter ; Wijermans, Pierre W. ; Lokhorst, Henk ; Goldschmidt, H. / Bortezomib Induction and Maintenance Treatment Improves Survival In Patients With Newly Diagnosed Multiple Myeloma:Extended Follow-Up Of The HOVON-65/GMMG-HD4 Trial. In: Blood. 2013 ; Vol. 122, No. 21. pp. 404-404.
@article{cb2eeb0541e740e38115b33914e3438f,
title = "Bortezomib Induction and Maintenance Treatment Improves Survival In Patients With Newly Diagnosed Multiple Myeloma:Extended Follow-Up Of The HOVON-65/GMMG-HD4 Trial",
abstract = "Background We investigated if bortezomib during induction and maintenance improves survival in newly diagnosed Multiple Myeloma (MM).\r\n\r\nMethods 827 eligible patients with newly diagnosed symptomatic MM were randomized to receive induction therapy with VAD (vincristine, doxorubicin, dexamethasone; n=414) or PAD (bortezomib, doxorubicin, dexamethasone; n=413) followed by high-dose melphalan (HDM) and autologous stem cell transplant (ASCT). Maintenance consisted of daily thalidomide 50 mg (VAD) or 2-weekly bortezomib 1.3 mg/m2 i.v. (PAD) for 2 years. The primary analysis was progression-free survival (PFS) adjusted for ISS stage. We here report long-term results of this trial ( P. Sonneveld et al., J Clin Oncol 2012;30:2946-2955 ).\r\n\r\nResults The number of eligible patients, patient characteristics and disease characteristics are similar to those reported before. The response rates during protocol treatment have improved slightly since all patients have now completed treatment: CR+nCR 49{\%} vs 35{\%}, VGPR 26{\%} vs 21{\%} and ≥PR 91{\%} vs 83{\%} (PAD vs VAD).\r\n\r\nAfter a median follow-up of 67 months, 111 of patients treated with VAD and 131 of patients treated with PAD were progression-free and alive. Progression-free survival (PFS) defined as time from randomization until progression, relapse or death (censored at date of alloSCT, if applicable), was superior with PAD when adjusted for ISS, (HR=0.78, 95{\%} CI [0.66-0.91], P=.002) and in multivariate analysis (HR=0.76 (95{\%} CI [0.64-0.90], P=.001). For the secondary endpoint overall survival (OS) the PAD arm was superior when adjusted for ISS (HR=0.80, 95{\%} CI [0.65-1.00], P=.047) as well as in multivariate analysis (HR=0.78, 95{\%} CI [0.63-0.97], P=.027). Landmark analysis from start of maintenance for PFS did not show a significant difference between Thalidomide and Bortezomib maintenance, however, for OS the PAD arm was superior (P=.035) (HR=0.71, 95{\%} CI [0.52-0.98]). Subgroup analysis performed on patients with renal failure at presentation (serum creatinine ≥2 mg/dL; 45 VAD, 36 PAD) showed that the PAD arm was significantly superior for PFS (HR=0.44, 95{\%} CI [0.26-0.75], P=.003) and OS (HR=0.38, 95{\%} CI [0.21-0.69], P",
author = "Christof Scheid and Holt, {Bronno van der} and Jarari, {Laila el} and Uta Bertsch and Hans Salwender and Sonja Zweegman and Edo Vellenga and Annemiek Broyl and Blau, {Igor Wolfgang} and Katja Weisel and Shulamit Wittebol and Bos, {Gerard M.J.} and Marjan Stevens and Schmidt-Wolf, {Ingo GH} and Michael Pfreundschuh and Dirk Hose and Anna Jauch and Velde, {Helgi van de} and Reinier Raymakers and Schaafsma, {Martyn Ronald} and Kersten, {Marie Jose} and Kooy, {Marinus van Marwijk} and Ulrich Duehrsen and Lindemann, {Hans Walter} and Wijermans, {Pierre W.} and Henk Lokhorst and H. Goldschmidt",
year = "2013",
language = "English",
volume = "122",
pages = "404--404",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "21",

}

Scheid, C, Holt, BVD, Jarari, LE, Bertsch, U, Salwender, H, Zweegman, S, Vellenga, E, Broyl, A, Blau, IW, Weisel, K, Wittebol, S, Bos, GMJ, Stevens, M, Schmidt-Wolf, IGH, Pfreundschuh, M, Hose, D, Jauch, A, Velde, HVD, Raymakers, R, Schaafsma, MR, Kersten, MJ, Kooy, MVM, Duehrsen, U, Lindemann, HW, Wijermans, PW, Lokhorst, H & Goldschmidt, H 2013, 'Bortezomib Induction and Maintenance Treatment Improves Survival In Patients With Newly Diagnosed Multiple Myeloma:Extended Follow-Up Of The HOVON-65/GMMG-HD4 Trial' Blood, vol. 122, no. 21, pp. 404-404.

Bortezomib Induction and Maintenance Treatment Improves Survival In Patients With Newly Diagnosed Multiple Myeloma:Extended Follow-Up Of The HOVON-65/GMMG-HD4 Trial. / Scheid, Christof; Holt, Bronno van der; Jarari, Laila el; Bertsch, Uta; Salwender, Hans; Zweegman, Sonja; Vellenga, Edo; Broyl, Annemiek; Blau, Igor Wolfgang; Weisel, Katja; Wittebol, Shulamit; Bos, Gerard M.J.; Stevens, Marjan; Schmidt-Wolf, Ingo GH; Pfreundschuh, Michael; Hose, Dirk; Jauch, Anna; Velde, Helgi van de; Raymakers, Reinier; Schaafsma, Martyn Ronald; Kersten, Marie Jose; Kooy, Marinus van Marwijk; Duehrsen, Ulrich; Lindemann, Hans Walter; Wijermans, Pierre W.; Lokhorst, Henk; Goldschmidt, H.

In: Blood, Vol. 122, No. 21, 2013, p. 404-404.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Bortezomib Induction and Maintenance Treatment Improves Survival In Patients With Newly Diagnosed Multiple Myeloma:Extended Follow-Up Of The HOVON-65/GMMG-HD4 Trial

AU - Scheid, Christof

AU - Holt, Bronno van der

AU - Jarari, Laila el

AU - Bertsch, Uta

AU - Salwender, Hans

AU - Zweegman, Sonja

AU - Vellenga, Edo

AU - Broyl, Annemiek

AU - Blau, Igor Wolfgang

AU - Weisel, Katja

AU - Wittebol, Shulamit

AU - Bos, Gerard M.J.

AU - Stevens, Marjan

AU - Schmidt-Wolf, Ingo GH

AU - Pfreundschuh, Michael

AU - Hose, Dirk

AU - Jauch, Anna

AU - Velde, Helgi van de

AU - Raymakers, Reinier

AU - Schaafsma, Martyn Ronald

AU - Kersten, Marie Jose

AU - Kooy, Marinus van Marwijk

AU - Duehrsen, Ulrich

AU - Lindemann, Hans Walter

AU - Wijermans, Pierre W.

AU - Lokhorst, Henk

AU - Goldschmidt, H.

PY - 2013

Y1 - 2013

N2 - Background We investigated if bortezomib during induction and maintenance improves survival in newly diagnosed Multiple Myeloma (MM).\r\n\r\nMethods 827 eligible patients with newly diagnosed symptomatic MM were randomized to receive induction therapy with VAD (vincristine, doxorubicin, dexamethasone; n=414) or PAD (bortezomib, doxorubicin, dexamethasone; n=413) followed by high-dose melphalan (HDM) and autologous stem cell transplant (ASCT). Maintenance consisted of daily thalidomide 50 mg (VAD) or 2-weekly bortezomib 1.3 mg/m2 i.v. (PAD) for 2 years. The primary analysis was progression-free survival (PFS) adjusted for ISS stage. We here report long-term results of this trial ( P. Sonneveld et al., J Clin Oncol 2012;30:2946-2955 ).\r\n\r\nResults The number of eligible patients, patient characteristics and disease characteristics are similar to those reported before. The response rates during protocol treatment have improved slightly since all patients have now completed treatment: CR+nCR 49% vs 35%, VGPR 26% vs 21% and ≥PR 91% vs 83% (PAD vs VAD).\r\n\r\nAfter a median follow-up of 67 months, 111 of patients treated with VAD and 131 of patients treated with PAD were progression-free and alive. Progression-free survival (PFS) defined as time from randomization until progression, relapse or death (censored at date of alloSCT, if applicable), was superior with PAD when adjusted for ISS, (HR=0.78, 95% CI [0.66-0.91], P=.002) and in multivariate analysis (HR=0.76 (95% CI [0.64-0.90], P=.001). For the secondary endpoint overall survival (OS) the PAD arm was superior when adjusted for ISS (HR=0.80, 95% CI [0.65-1.00], P=.047) as well as in multivariate analysis (HR=0.78, 95% CI [0.63-0.97], P=.027). Landmark analysis from start of maintenance for PFS did not show a significant difference between Thalidomide and Bortezomib maintenance, however, for OS the PAD arm was superior (P=.035) (HR=0.71, 95% CI [0.52-0.98]). Subgroup analysis performed on patients with renal failure at presentation (serum creatinine ≥2 mg/dL; 45 VAD, 36 PAD) showed that the PAD arm was significantly superior for PFS (HR=0.44, 95% CI [0.26-0.75], P=.003) and OS (HR=0.38, 95% CI [0.21-0.69], P

AB - Background We investigated if bortezomib during induction and maintenance improves survival in newly diagnosed Multiple Myeloma (MM).\r\n\r\nMethods 827 eligible patients with newly diagnosed symptomatic MM were randomized to receive induction therapy with VAD (vincristine, doxorubicin, dexamethasone; n=414) or PAD (bortezomib, doxorubicin, dexamethasone; n=413) followed by high-dose melphalan (HDM) and autologous stem cell transplant (ASCT). Maintenance consisted of daily thalidomide 50 mg (VAD) or 2-weekly bortezomib 1.3 mg/m2 i.v. (PAD) for 2 years. The primary analysis was progression-free survival (PFS) adjusted for ISS stage. We here report long-term results of this trial ( P. Sonneveld et al., J Clin Oncol 2012;30:2946-2955 ).\r\n\r\nResults The number of eligible patients, patient characteristics and disease characteristics are similar to those reported before. The response rates during protocol treatment have improved slightly since all patients have now completed treatment: CR+nCR 49% vs 35%, VGPR 26% vs 21% and ≥PR 91% vs 83% (PAD vs VAD).\r\n\r\nAfter a median follow-up of 67 months, 111 of patients treated with VAD and 131 of patients treated with PAD were progression-free and alive. Progression-free survival (PFS) defined as time from randomization until progression, relapse or death (censored at date of alloSCT, if applicable), was superior with PAD when adjusted for ISS, (HR=0.78, 95% CI [0.66-0.91], P=.002) and in multivariate analysis (HR=0.76 (95% CI [0.64-0.90], P=.001). For the secondary endpoint overall survival (OS) the PAD arm was superior when adjusted for ISS (HR=0.80, 95% CI [0.65-1.00], P=.047) as well as in multivariate analysis (HR=0.78, 95% CI [0.63-0.97], P=.027). Landmark analysis from start of maintenance for PFS did not show a significant difference between Thalidomide and Bortezomib maintenance, however, for OS the PAD arm was superior (P=.035) (HR=0.71, 95% CI [0.52-0.98]). Subgroup analysis performed on patients with renal failure at presentation (serum creatinine ≥2 mg/dL; 45 VAD, 36 PAD) showed that the PAD arm was significantly superior for PFS (HR=0.44, 95% CI [0.26-0.75], P=.003) and OS (HR=0.38, 95% CI [0.21-0.69], P

M3 - Article

VL - 122

SP - 404

EP - 404

JO - Blood

JF - Blood

SN - 0006-4971

IS - 21

ER -