Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma

Abstract

Bortezomib plus melphalan-prednisone was superior to melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)

Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma

“…Both bortezomib 42,43 and thalidomide [44][45][46] are associated with peripheral neuropathy, so a possible increase in the incidence of peripheral neuropathy when these agents are combined was a concern with BTD therapy. However, the 45% rate of neuropathy reported in our analysis appears similar to that reported with bortezomib plus melphalan and prednisone in previously untreated patients in the VISTA phase 3 study (44%) 4 and with single-agent bortezomib in the Assessment of Proteasome Inhibition on Extending Remissions (APEX) phase 3 study (37%) 43 ; the 9% rate of grade 3 events also appears similar to the rates reported in VISTA (13%) 4 and APEX (9%), 43 in the GIMEMA phase 3 study of BTD (9%), 13 in the IFM phase 3 study of bortezomib plus dexamethasone (7%), 38 and in phase 3 studies of thalidomide plus dexamethasone (3%-7%). 5,6 Together, these data suggest that the combination of bortezomib and thalidomide in the BTD regimen does not appear to result in additive peripheral neuropathy.…”

A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end‐stage renal disease requiring haemodialysis

“…Therefore, an understanding of the impact of RI on the PK of a drug used to treat MM is important to inform appropriate dosing, in order to ensure safe and effective pharmacotherapy. Several subanalyses and studies suggest that treatment with bortezomib‐based therapy is effective and well tolerated in MM patients with RI and can at least partially overcome the negative prognostic impact of RI in these patients (San Miguel et al , 2008; Dimopoulos et al , 2010; Ludwig et al , 2010; Morabito et al , 2011; Scheid et al , 2014). Carfilzomib has also demonstrated clinical efficacy in RRMM patients with varying degrees of RI (CrCl 50–80 ml/min, 30–49 ml/min, <30 ml/min and chronic haemodialysis) in a phase 2 study, and the safety and PK properties of carfilzomib did not appear to be influenced by the level of baseline RI (Badros et al , 2013).…”

“…MM‐associated RI presents distinct therapeutic challenges and, in its severe forms, is predictive of a poorer prognosis (Gonsalves et al , 2015; Khan et al , 2015; Laing et al , 2015). Previous studies suggest that the currently available PIs, bortezomib and carfilzomib, are effective and well tolerated in MM patients with varying degrees of RI (San Miguel et al , 2008; Chanan‐Khan et al , 2012; Badros et al , 2013). Accumulating evidence also suggests that bortezomib may even reverse RI or renal failure in MM (Dimopoulos et al , 2009a,b; Ludwig et al , 2010; Moreau et al , 2015b).…”

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

“…In a large Phase III trial, VMP demonstrated better OS compared with MP [78,79]. There is a suggestion that VMP can overcome some high-risk cytogenetic features [79].…”

“…Substituting melphalan with thalidomide in the VMP regimen has not shown an advantage; in a randomized trial, bortezomib, thalidomide, prednisone (VTP) was not superior to VMP [65]. Neuropathy is a significant risk with VMP therapy when bortezomib is administered in the usual twice weekly schedule; Grade 3 neuropathy occurred in 13% of patients versus 0% with MP [78]. This rate can be greatly decreased by administering bortezomib using a once-weekly schedule [65,66].…”