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BACKGROUND Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. METHODS In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently.(More)
PURPOSE To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma. PATIENTS AND METHODS Peripheral neuropathy was assessed in two phase II studies in 256 patients with relapsed and/or refractory myeloma treated with bortezomib 1.0 or 1.3 mg/m2 intravenous bolus on days 1,(More)
Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the(More)
Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m(2) intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m(2) for ≤ 12 cycles. The(More)
In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1.0 or 1.3 mg/m(2) bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with(More)
BACKGROUND Lenalidomide, an oral immunomodulatory drug that is similar to thalidomide but has a different safety profile, has clinical activity in relapsed or refractory multiple myeloma. METHODS Patients in the United States and Canada who had received at least one previous therapy for multiple myeloma but who required additional treatment were randomly(More)
NAD(P)H: quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme, important in the detoxification of environmental carcinogens. A single base substitution (C --> T) polymorphism at nucleotide 609 (null-allele) of NQO1 gene impairs stability and function of the NQO1 protein. To investigate the association of this NQO1 polymorphism with susceptibility to(More)
We previously reported a phase 1b dose-escalation study of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) in relapsed or progressive multiple myeloma where the maximum planned dose (MPD) was carfilzomib 20 mg/m2 days 1 and 2 of cycle 1 and 27 mg/m2 days 8, 9, 15, 16, and thereafter; lenalidomide 25 mg days 1 to 21; and dexamethasone 40 mg once(More)
It is essential that there be consistency in the conduct, analysis, and reporting of clinical trial results in myeloma. The goal of the International Myeloma Workshop Consensus Panel 1 was to develop a set of guidelines for the uniform reporting of clinical trial results in myeloma. This paper provides a summary of the current response criteria in myeloma,(More)
Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were(More)