The final analysis of the phase 3 VISTA trial upheld a persistent and significant survival benefit for bortezomib in patients with previously untreated multiple myeloma.
Of the 655 patients in VISTA, those treated with bortezomib lived an average of 13.3 months longer than those receiving a regimen lacking this agent, VISTA investigator Jesús F. San Miguel, MD, PhD, of the Hospital Clinico Universitario, Salamanca, Spain, reported.
“An overall survival [OS] benefit was seen across multiple prespecified patient subgroups and was maintained after 5 years’ follow-up and despite substantial use of novel agent–based salvage therapies,” said Dr San Miguel.
Data from the initial report of this international phase 3 trial showed that nine 6-week cycles of the bortezomib, melphalan, and prednisone (VMP) regimen were superior to the melphalan and prednisone (MP) regimen in patients with previously untreated multiple myeloma. At 36.7 months of follow-up, a second analysis confirmed a continued OS benefit. The current report was the final updated OS analysis after 5 years of follow-up, which includes data on 95% of the original cohort.
The 5-year follow-up also found no association between bortezomib treatment and the development of second primary cancers, at least above and beyond the incidence of cancer in the general healthy population. Since reports surfaced at ASH last year that lenalidomide seemed to be associated with a higher risk for second malignancies, studies of myeloma therapies all examine this potential risk.
Dr San Miguel said that based on the findings of no excess cancers, he is convinced that the long-term use of bortezomib is “completely safe.”
5-Year Mortality Risk Reduced by 31%
Mortality risk was reduced by 31% with the addition of bortezomib to the treatment regimen, despite the significant use of subsequent therapy once the disease progressed.
Median OS was 56.4 months after treatment with VMP versus 43.1 months with MP, amounting to an absolute benefit of 13.3 additional months of life across all subgroups (P = .004). The OS rate at 5 years was 46.0% with VMP versus 34.4% with MP, Dr San Miguel said.
Virtually all subgroups benefited significantly from the addition of bortezomib, including:
- Older patients age ≥75 years, who had a 29% reduction in risk of death
- Patients with International Staging System stage III disease, who had a 23% risk reduction
- Patients with creatinine clearance <60 mL/min, who had a 30% risk reduction.
Only the small subgroup of patients with documented high-risk cytogenetics had no additional benefit from bortezomib.
Bortezomib also added 8 additional months to the time before the next treatment was required, and extended the treatment-free interval by almost 8 months (P <.001 for both).
As for the best time to prescribe bortezomib to previously untreated patients, Dr San Miguel noted that patients who received bortezomib as first-line treatment had longer OS than those who received bortezomib or other therapies in subsequent treatment lines. “These findings demonstrate the importance of providing optimal first-line treatment incorporating bortezomib,” he said, “rather than reserving bortezomib for salvage therapy and using conventional first-line treatment.”