title: Bortezomib before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in newly diagnosed multiple myeloma: a subgroup analysis from the HOVON-65/GMMG-HD4 trial.
abstract: Renal impairment is frequent in patients with multiple myeloma and is correlated with an inferior prognosis. This analysis evaluates the prognostic role of renal impairment in patients with myeloma treated with bortezomib before and after autologous stem cell transplantation within a prospective randomized phase III trial. Eight hundred and twenty-seven newly diagnosed myeloma patients in the HOVON-65/GMMG-HD4 trial were randomized to receive three cycles of vincristine, adriamycin, dexamethasone (VAD) or bortezomib, adriamycin, dexamethasone (PAD) followed by autologous stem cell transplantation and maintenance with thalidomide 50 mg daily (VAD-arm) or bortezomib 1.3 mg/m(2) every 2 weeks (PAD-arm). Baseline serum creatinine was less than 2 mg/dL (Durie-Salmon-stage A) in 746 patients and 2 mg/dL or higher (stage B) in 81. In myeloma patients with a baseline creatinine ≥ 2 mg/dL the renal response rate was 63% in the VAD-arm and 81% in the PAD-arm (P=0.31). The overall myeloma response rate was 64% in the VAD-arm versus 89% in the PAD-arm with 13% complete responses in the VAD-arm versus 36% in the PAD-arm (P=0.01). Overall survival at 3 years for patients with a baseline creatinine ≥ 2 mg/dL was 34% in the VAD-arm versus 74% in the PAD-arm (P<0.001) with a progression-free survival rate at 3 years of 16% in the VAD-arm versus 48% in the PAD-arm (P=0.004). Overall and progression-free survival rates in the PAD-arm were similar in patients with a baseline creatinine ≥ 2 mg/dL or <2 mg/dL. We conclude that a bortezomib-containing treatment before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in patients with newly diagnosed multiple myeloma. The trial was registered at www.trialregister.nl as NTR213 and at www.controlled-trials.com as ISRCTN 64455289.
authors.affiliation: c.scheid@uni-koeln.de.
authors.forename: Christof
authors.initials: C
authors.lastname: Scheid
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Laila
authors.initials: L
authors.lastname: el Jarari
authors.forename: Uta
authors.initials: U
authors.lastname: Bertsch
authors.forename: Hans
authors.initials: H
authors.lastname: Salwender
authors.forename: Sonja
authors.initials: S
authors.lastname: Zweegman
authors.forename: Igor Wolfgang
authors.initials: IW
authors.lastname: Blau
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Katja
authors.initials: K
authors.lastname: Weisel
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Kon-Siong
authors.initials: KS
authors.lastname: Jie
authors.forename: Kai
authors.initials: K
authors.lastname: Neben
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Ulrich
authors.initials: U
authors.lastname: Duehrsen
authors.forename: M Ron
authors.initials: MR
authors.lastname: Schaafsma
authors.forename: Walter
authors.initials: W
authors.lastname: Lindemann
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Kersten
authors.forename: Norma
authors.initials: N
authors.lastname: Peter
authors.forename: Mathias
authors.initials: M
authors.lastname: Hänel
authors.forename: Sandra
authors.initials: S
authors.lastname: Croockewit
authors.forename: Hans
authors.initials: H
authors.lastname: Martin
authors.forename: Shulamiet
authors.initials: S
authors.lastname: Wittebol
authors.forename: Gerard Mj
authors.initials: GM
authors.lastname: Bos
authors.forename: Marinus
authors.initials: M
authors.lastname: van Marwijk-Kooy
authors.forename: Pierre
authors.initials: P
authors.lastname: Wijermans
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Henk M
authors.initials: HM
authors.lastname: Lokhorst
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D003404:Creatinine / Q000097:blood; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000401:mortality / Q000628:therapy*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D051437:Renal Insufficiency / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003404:Creatinine