Bortezomib before & after high-dose therapy in myeloma: phase III HOVON-65/GMMG-HD4 trial
Updated: May 21, 2022
Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial
phase III HOVON-65/GMMG-HD4 trial.
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.
Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/ GMMG-HD4 Trial
Volume 30, Issue 24 - 2012
Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.
Full Title: A randomized phase III study on the effect of Bortezomib combined with Adriamycin, Dexamethasone (AD) for induction treatment, followed by High Dose Melphalan and Bortezomib alone during maintenanc...
Sponsor Protocol Number: HOVON 65 MM / GMMG-HD4
Start Date*: 2007-05-02
Sponsor Name:HOVON foundation
HOVON HO65 MM
To assess the efficacy of Bortezomib combined with intensive chemotherapy and in maintenance therapy in comparison with intensive therapy with Vincristine followed by thalidomide maintenance in patients with previously untreated multiple myeloma, as measured by the progression free survival as defined in chapter 14.
To evaluate the overall response rate and CR + VGPR (complete and very good partial response) both after induction therapy and after autologous transplant.
To evaluate overall survival.
To assess the safety and toxicity of Bortezomib combined with intensive chemotherapy and in maintenance therapy.
To assess the prognostic value of risk factors at diagnosis, including β2-microglobulin, karyotypic abnormalities of chromosomes 9, 11 and 13 as analyzed in bone marrow plasma cells by karyotyping and FISH, with respect to progression free survival.
To analyze the prognostic value of myeloma gene expression profiles on the overall response on induction of all patients and of patients treated with Bortezomib separately.
GMMG - The German Speaking Myeloma Multicenter Group