Higher Bortezomib Dose Upped Multiple Myeloma Survival

Ball-and-stick model of bortezomib

Patients with treatment-naive, transplant-ineligible multiple myeloma who received a higher cumulative bortezomib dose, either through higher dose intensity or prolonged treatment, as part of a bortezomib/melphalan/prednisone (VMP) regimen, had significantly improved overall survival, according to results of an analysis using data from the phase III VISTA study.

“The observed association between cumulative bortezomib dose and overall survival is consistent with previous suggestions of improved clinical outcomes with increased bortezomib exposure,” wrote Maria-Victoria Mateos, MD, PhD, of the Instituto Biosanitario de Salamanca, Spain, and colleagues in the American Journal of Hematology.

“Several strategies could be used to achieve a higher cumulative bortezomib dose in clinical practice, including the use of subcutaneous bortezomib administration, bortezomib administration only once per week, continued therapy in patients benefiting from treatment, and proactive adverse event management,” the researchers wrote.

In this analysis, Mateos and colleagues compared overall survival in patients who received more or less than the median cumulative bortezomib dose (39 mg/m²) received by 340 patients in the VISTA study.

Results showed that those patients who received higher than the median had a significantly longer overall survival compared with those patients who received a dose less than the median. Median overall survival was 66.3 months in the higher dose group compared with 46.2 months in the lower dose group (P < .0001). The improvement in overall survival remained even after adjustment for age, which was the only significant baseline difference between the two study groups.

“To overcome confounding effects of early discontinuation/deaths, which were more common in the lower cumulative dose group, a landmark analysis was conducted at 180 days, eliminating patients who died or discontinued before this time from the analysis,” the researchers wrote.

Despite this adjustment, the patients with the higher cumulative dose had a significantly improved median overall survival of 60.4 months compared with 50.3 months for patients with the lower cumulative dose (P = .0372).

Patients had similar rates of treatment-related adverse events regardless of the cumulative bortezomib dose. The researchers did find that fewer patients in the higher dose groups had serious adverse events compared with those in the lower dose group (35% vs 58%).