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Effect of cumulative bortezomib dose on survival in multiple myeloma patients receiving bortezomib‐melphalan‐prednisone in the phase III VISTA study
Author(s) -
Mateos María Victoria,
Richardson Paul G.,
Dimopoulos Meletios A.,
Palumbo Antonio,
Anderson Kenneth C.,
Shi Hongliang,
Elliott Jennifer,
Dow Edward,
van de Velde Helgi,
Niculescu Liviu,
San Miguel Jesús F.
Publication year - 2015
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23933
Subject(s) - cumulative dose , bortezomib , medicine , multiple myeloma , melphalan , cumulative incidence , prednisone , adverse effect , hazard ratio , surgery , gastroenterology , cohort , confidence interval
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. © 2015 Wiley Periodicals, Inc.