Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myeloma.

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PURPOSE: To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN). PATIENTS AND METHODS: We analyzed DNA from 1,495 patients with multiple myeloma. Using a custom-built single nucleotide polymorphism (SNP) array, we tested the association of TrPN with 3,404 SNPs. The SNPs were selected in predicted functional regions within 964 genes spanning 67 molecular pathways thought to be involved in the pathogenesis, treatment response, and adverse effects associated with myeloma and its therapy. Patient cases and controls were derived from two large clinical trials that compared thalidomide with conventional-based treatment in myeloma patients (Medical Research Council Myeloma-IX and HOVON-50/GMMG-HD3). RESULTS: We report TrPN […]

Genetic predisposition for chemotherapy-induced neuropathy in multiple myeloma

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Peripheral neuropathy is one of the most frequent and debilitating adverse effects encountered by patients with cancer undergoing chemotherapy treatment. For multiple myeloma (MM), every effective regimen includes at least one agent that can cause neuropathy, a major dose-limiting toxicity in clinical trials and in clinical practice. Furthermore, neuropathy occurs even before therapy as a consequence of the disease in approximately 20% of patients with MM, and can even occur in the precursor condition, monoclonal gammopathy of undetermined significance. Authors: Becker p. et al. J Clin Oncol. 2011 Mar 1;29(7):783-6. doi: 10.1200/JCO.2010.33.4771. Epub 2011 Jan 18. Click here to view Article

International Myeloma Working Group (IMWG) Molecular Classification of Multiple Myeloma

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The intent of this statement is to provide a biological classification of multiple myeloma and to establish the prognostic value of known genetic factors. Myeloma is divided at the highest genetic level into two subtypes: disease that is hyperdiploid (h-MM), and disease that is non-hyperdiploid (nh-MM). The non-hyperdiploid type is characterized by immunoglobulin heavy-chain (IgH) translocations and is generally associated with more aggressive disease and shorter survival. Accurate prognostic determination of disease course allows for a more rational selection and sequencing of therapy approaches and more direct discussion with the patient regarding disease threat. Risk stratification is essential for better understanding of the composition of patients in clinical trials, and […]