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
SN - 0006-4971
VL - 122
SP - 404
EP - 404
JO - Blood
JF - Blood
IS - 21
ER -