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: Christof Scheid, Pieter Sonneveld, Ingo G H Schmidt-Wolf, Bronno van der Holt, Laila el Jarari, Uta Bertsch, Hans Salwender, Sonja Zweegman, Igor Wolfgang Blau, Edo Vellenga, Katja Weisel, Michael Pfreundschuh, Kon-Siong Jie, Kai Neben, Helgi van de Velde, Ulrich Duehrsen, M Ron Schaafsma, Walter Lindemann, Marie José Kersten, Norma Peter, Mathias Hänel, Sandra Croockewit, Hans Martin, Shulamiet Wittebol, Gerard Mj Bos, Marinus van Marwijk-Kooy, Pierre Wijermans, Hartmut Goldschmidt, Henk M Lokhorst
• Journal: Haematologica (Haematologica) Vol. 99 Issue 1 Pg. 148-54 (Jan 2014) ISSN: 1592-8721 [Electronic] Italy
• PMID: 23996482 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Boronic Acids
• Pyrazines
• Bortezomib
• Creatinine

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Boronic Acids (administration & dosage, adverse effects, therapeutic use)
• Bortezomib
• Creatinine (blood)
• Hematopoietic Stem Cell Transplantation
• Humans
• Middle Aged
• Multiple Myeloma (complications, mortality, therapy)
• Pyrazines (administration & dosage, adverse effects, therapeutic use)
• Remission Induction
• Renal Insufficiency (etiology, mortality, physiopathology, prevention & control)
• Transplantation, Autologous
• Treatment Outcome