International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease

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PURPOSE: The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) -related bone disease. METHODOLOGY: An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members. RECOMMENDATIONS: Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage […]

Management of treatment-emergent peripheral neuropathy in multiple myeloma

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Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology oftreatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent […]

IMWG Guidelines for the Management of Treatment-Emergent Peripheral Neuropathy in Multiple Myeloma (MM)

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The incidence, symptoms, reversibility, and predisposing factors of treatment-emergent peripheral neuropathy (PN) vary among myeloma therapies. PN incidence is affected by treatment dose and schedule, by combinations of potentially neurotoxic agents, and by patient characteristics. Strategies for managing PN include early and regular monitoring, dose modification, and treatment discontinuation. Because there is no cure for drug-induced PN, prevention is a key strategy for preserving quality of life and future treatment options. Following are evidence-based guidelines for preventing, assessing, and treating PN. PREVENTION OF PN The optimal prevention of treatment-induced PN in MM patients can be achieved with careful dose modification of the treatments that cause it, chiefly bortezomib and thalidomide. […]

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

Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial

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Bortezomib-induced peripheral neuropathy is a dose-limiting toxicity in patients with multiple myeloma, often requiring adjustment of treatment and affecting quality of life. We investigated the molecular profiles of early-onset (within one treatment cycle) versus late-onset (after two or three treatment cycles) bortezomib-induced peripheral neuropathy and compared them with those of vincristine-induced peripheral neuropathy during the induction phase of a prospective phase 3 trial. Authors: Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y, van Duin M, el Jarari L, Bertsch U, Lokhorst HM, Durie BG, Goldschmidt H, Sonneveld P Lancet Oncol. 2010 Nov;11(11):1057-65. doi: 10.1016/S1470-2045(10)70206-0. Epub 2010 Sep 21 Click here to view Article

Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group

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Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light […]

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

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Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino- and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and […]

IMWG Guidelines for the Prevention of Thalidomide- and Lenalidomide-Associated Thrombosis in Myeloma

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The risk of VTE in cancer patients is greater than 7%; those with myeloma have the highest risk of thrombosis.2 The oral immunomodulatory drugs, thalidomide and lenalidomide, further increase that risk. The following guidelines from the International Myeloma Working Group recommend a prophylaxis strategy based upon a risk assessment model. The recommendations have been made in the absence of clear data from randomized studies, and are therefore based on common sense and on data extrapolated from many studies not specifically designed to answer these questions. Treatment decisions must be based on the type of therapy and the patientís individual risk factors. Risk factors for venous thromboembolism (VTE) in myeloma patients […]

Survival and years of life lost in different age cohorts of patients with multiple myeloma

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PURPOSE: To assess the impact of age on outcome and to analyze the projected years of life lost in patients with multiple myeloma. PATIENTS AND METHODS: Ten thousand five hundred forty-nine patients were evaluated; 6,996 patients were treated with conventional chemotherapy, and 3,553 patients were treated with high-dose therapy with autologous stem-cell transplantation. RESULTS: Mean observed and relative overall survival times in the entire cohort were 3.7 and 3.9 years, respectively. Observed survival decreased steadily from 6.4 years in patients younger than age 50 years to 2.5 years in patients > or = age 80 years. A similar decrease was noted for relative survival. Higher age correlated significantly with higher […]