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 The International Myeloma Working Group, a collaborative group of leading myeloma specialists around the globe, has a two-fold task: to publish consensus statements and guidelines for the management of myeloma and to conduct translational research—from lab bench to patient bedside--under the auspices of the International Myeloma Foundation. The following publications represent both the work of the International Myeloma Working Group and the work of individual IMWG members who have based their papers on IMWG data sets that were made available to them.
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The prevalence of peripheral neuropathy (PNP) during the treatment of MM with Bortezomib is high.
About 20% of patients develop a grade 3-4 PNP due to this treatment, and as a result Bortezomib treatment is
stopped or a reduced dose is given. Therefore, there is a strong need to find markers which predict the
susceptibility of a patient to develop Bortezomib related PNP.
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Gareth Morgan, MD
Section of Haemato-Oncology
The Institute of Cancer Research
London, United Kingdom
Member, IMF Board of Scientific Advisors
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Gareth Morgan, MD
Section of Haemato-Oncology
The Institute of Cancer Research
London, United Kingdom
Member, IMF Board of Scientific Advisors
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Brian Van Ness, PhD
University of Minnesota
Institute of Human Genetics
Minneapolis, Minnesota
USA
Member, IMF Board of Scientific Advisors
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The proteasome inhibitor bortezomib has demonstrated high antitumor
activity in multiple myeloma (MM). Peripheral neuropathy (PNP) is a doselimiting toxicity of bortezomib, which typically occurs within the first cycles of bortezomib in 30-40% of MM patients. Although bortezomib induced PNP is manageable and reversible in most MM patients, no effective prophylactic treatment against PNP is available and bortezomib discontinuation is frequently required. Identifying patients at risk of neuropathy and understanding its pathogenesis is therefore of great importance.
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Multiple Myeloma (MM) is a plasma cell malignancy, characterized by
significant heterogeneous disease progression and response to therapy. It is very likely that genetic polymorphisms of genes involved in drug absorption, distribution, metabolism and excretion may affect a patient’s response to
therapy.
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Published in the Journal of Clinical Oncology, Volume 29, Number 7, March 1, 2011 |
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Editorial
Published in the Journal of Clinical Oncology, Volume 29, Number 7, March 1, 2011 |
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It is anticipated that inherited single nucleotide polymorphisms (SNPs) in genes involved in drug absorption, distribution, metabolism and excretion influence individual response to thalidomide therapies in Multiple Myeloma. We extracted peripheral blood DNA from 631 myeloma patients of European descent enrolled in the MRC Myeloma IX trial who had received induction thalidomide (50-200mg). We genotyped 3404 SNPs selected in 983 candidate genes that may influence myeloma disease response, toxicity, and/or survival, on a “Bank on a Cure” (BOAC) Affymetrix® true-tag array.
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We have engaged in an international program designated the Bank On A Cure, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma.
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Published in Lancet Oncol 2010; 11: 1057–65 |
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