Long-Term Data Confirm Efficacy of Bortezomib in Improving Overall Survival

Investigators strengthened the results of a 2012 trial with a long-term follow-up of an important phase III trial evaluating a bortezomib-based regimen versus a vincristine-based regimen.

Sonneveld et al compared the efficacy of 2 maintenance treatments in patients with newly diagnosed multiple myeloma in the phase III HOVON-65/GMMG-HD4 Trial. Initial results were published in August 2012 in the Journal of Clinical Oncology.

The phase III trial investigated the efficacy of an induction regimen and a maintenance regimen in multiple myeloma. For induction therapy, patients received either a vincristine-based regimen (vincristine, doxorubicin, and dexamethasone) or a bortezomib-based regimen (bortezomib, doxorubicin, and dexamethasone) followed by an autologous stem cell transplant. For the next 2 years, patients on the vincristine-based induction regimen received maintenance therapy with thalidomide and patients who received the bortezomib-based induction therapy (bortezomib, doxorubicin, and dexamethasone) received bortezomib for maintenance regimen.

In the initial trial, investigators found an improvement in progression-free survival (PFS) and overall survival (OS) over a median 41-month follow-up period. PFS was significantly longer in patients receiving bortezomib-based maintenance treatment than in patients receiving thalidomide (median PFS: 35 months versus 28 months, respectively; P = .002). OS was also significantly higher in the bortezomib-based treatment arm than the thalidomide-based maintenance arm (HR, 0.77; P = .049). However, the OS advantage of the bortezomib-based regimen was not statistically significant with adjustment for each patient’s international staging system rating (HR = 0.81, P = .11).

In an abstract presentation at the 2013 American Society for Hematology (ASH) annual meeting, Sonneveld and colleagues presented results updating the median 41-month follow-up that was published in 2012 with a median 67-month follow-up of trial results.

The long-term results strengthened the conclusions of the 2012 trial, confirming a significant advantage of bortezomib-based maintenance treatment over lenolidomide maintenance treatment in PFS, both in multivariable analysis (HR = 0.78; P = .002) and in an analysis adjusting for each patient’s international staging system rating (HR = 0.76; P = .001). The long-term results also confirmed a significant benefit of bortezomib-based treatment over thalidomide-based maintenance treatment in OS both in the multivariate analysis (HR = 0.78, P = .027) and in an analysis adjusting for each patient’s international staging system rating (HR = 0.80, P = .047).

The 67-month long-term results presented in the meeting abstract strengthened the initial results of the phase III trial and affirmed the superior efficacy of therapeutic combinations including bortezomib over other therapies in improving outcomes for patients with newly diagnosed multiple myeloma.