Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 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

Research output: Contribution to journalArticleAcademicpeer-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 languageEnglish
Pages (from-to)383-390
Number of pages8
JournalLeukemia
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 2018

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