Analysis: Increased OS with higher cumulative dose of bortezomib in patients with previously untreated multiple myeloma

January 9, 2014

A higher cumulative dose of bortezomib (Velcade, Millennium: The Takeda Oncology Company) suggested improved overall survival (OS) in previously untreated multiple myeloma patients, according to results from a retrospective subgroup analysis of the phase 3 VISTA study.

A higher cumulative dose of bortezomib (VELCADE, Millennium: The Takeda Oncology Company) suggested improved overall survival (OS) in previously untreated multiple myeloma patients, according to results from a retrospective subgroup analysis of the phase 3 VISTA study.

The analysis, presented at the American Society of Hematology (ASH) 2013 annual meeting in New Orleans, showed that patients who received a cumulative dose of bortezomib of 39 mg/m2 or greater lived 20 months longer on average than those who received lower cumulative doses (median OS 66.3 months and 46.2 months, respectively).

Specifically, the analysis, presented by María-Victoria Mateos, MD, Hospital Universitario, Salamanca, Salamanca, Spain, used data from the VMP (VELCADE-melphalan-prednisone) arm of the VISTA study. VISTA evaluated the efficacy of a VMP regimen of up to 54 weeks in transplant-ineligible patients with previously untreated multiple myeloma.

Patients (n=340) treated with the VMP regimen in VISTA received up to 9 six-week cycles (up to 54 weeks) of the combination therapy (cycles 1-4: bortezomib 1.3 mg/m2 IV, days 1, 4, 8, 11, 22, 25, 29, 32; cycles 5-9: bortezomib 1.3 mg/m2 IV, days 1, 8, 22, 29; all cycles: melphalan 9 mg/m2 and prednisone 60 mg/m2).

·      The maximum planned dose of bortezomib was 67.6 mg/m2, including 41.6 mg/m2 during cycles 1-4 and 26 mg/m2 during cycles 5-9.

·      The median cumulative bortezomib dose received was 39 mg/m2, which was selected as the cut-off point for defining patient groups by cumulative bortezomib dose for analyses of OS.

A landmark analysis of OS from 180 days after the first dose to approximately align with cycles 1-4 of the study was conducted.

The analysis was conducted to determine whether increased cumulative bortezomib dose-obtained by longer treatment duration, more intensive therapy, or both-led to better long-term patient outcomes.

Although clinical trials provide some guidance on the duration of bortezomib treatment, there is no widely accepted clinical guidance on the optimal treatment duration. The correlation between cumulative dose--taking into account both actual dose and time on therapy-and OS has not been assessed.

"VISTA showed an overall survival benefit in multiple myeloma and it reinforces the importance of treating patients with a 12-month course of [bortezomib] therapy,” said Dr Mateos. "This subgroup analysis, while retrospective, suggests that patients who received a dose of 39 mg/m2 or greater fared better than those who received a lesser dose."