Περίληψη:
This analysis, using data from the bortezomib-melphalan-prednisone (VMP)
arm of the Phase III VISTA study, investigated whether increased
cumulative bortezomib dose could improve overall survival (OS) in
transplant-ineligible patients with previously untreated multiple
myeloma. Median cumulative bortezomib dose received by the 340 patients
was 39 mg/m(2); this was selected as the cut-off for defining the dose
groups to be compared for OS. Patient characteristics were well balanced
between dose groups except for age. OS was significantly longer in the
higher (39 mg/m(2)) versus lower (<39 mg/m(2)) cumulative bortezomib
dose group (median 66.3 vs. 46.2 months; hazard ratio (HR) 0.533,
P<0.0001; age-adjusted HR 0.561, P=0.0002). To overcome confounding
effects of early discontinuations/deaths, which were more common in the
lower cumulative dose group (27 vs. 4% of patients discontinued due to
adverse events (AEs) in the lower and higher cumulative dose groups,
respectively), a landmark analysis was conducted at 180 days,
eliminating patients who died or discontinued before this time from the
analysis. OS from this landmark remained significantly longer in the
higher dose group (median 60.4 vs. 50.3 months; HR 0.709, P=0.0372).
Thus, higher cumulative bortezomib dose, reflecting prolonged treatment
duration and/or dose intensity, appears associated with improved OS.
Approaches to achieve higher cumulative doses could include subcutaneous
bortezomib administration, dose/schedule modifications, continuing
therapy in responding patients, and proactive AE management. Am. J.
Hematol. 90:314-319, 2015. (c) 2015 Wiley Periodicals, Inc.
Συγγραφείς:
Victoria Mateos, Maria
Richardson, Paul G.
Dimopoulos, Meletios
A.
Palumbo, Antonio
Anderson, Kenneth C.
Shi, Hongliang and
Elliott, Jennifer
Dow, Edward
van de Velde, Helgi
Niculescu,
Liviu
San Miguel, Jesus F.
