Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial

作者：Goldschmidt H^*; Lokhorst H M; Mai E K; van der Holt B; Blau I W; Zweegman S; Weisel K C; Vellenga E; Pfreundschuh M; Kersten M J; Scheid C; Croockewit S; Raymakers R; Hose D; Potamianou A; Jauch A; Hillengass J; Stevens Kroef M; Raab M S; Broijl A; Lindemann H W; Bos G M J; Brossart P; Kooy M van Marwijk; Ypma P; Duehrsen U; Schaafsma R M; Bertsch U; Hielscher T; Jarari Le; Salwender H J; Sonneveld P

来源：Leukemia, 2018, 32(2): 383-390.

DOI：10.1038/leu.2017.211

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.

• 出版日期2018-2