Bortezomib before and after high-dose therapy in myeloma
Long-term results from the phase III HOVON-65/GMMG-HD4 trial
Leukemia , Volume 32 - Issue 2 p. 383- 390
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.
|Parts of this manuscript have been presented at the 2015 ASH Annual Meeting, Orlando, Florida|
|Organisation||Department of Hematology|
Goldschmidt, H, Lokhorst, H.M, Mai, E.K. (E. K.), van der Holt, B, Blau, I.W, Zweegman, S, … Sonneveld, P. (2018). Bortezomib before and after high-dose therapy in myeloma. Leukemia, 32(2), 383–390. doi:10.1038/leu.2017.211