Combining Fluorescent In Situ Hybridization (iFISH) data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group (IMWG) collaborative project

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The combination of serum b2-microglobulin and albumin levels has been shown to be highly prognostic in myeloma as the International Staging System (ISS). The aim of this study was to assess the independent contributions of ISS stage and cytogenetic abnormalities in predicting outcomes. A retrospective analysis of international studies looking at both ISS and cytogenetic abnormalities was performed in order to assess the potential role of combining ISS stage and cytogenetics to predict survival. This international effort used the International Myeloma Working Group database of 12 137 patients treated worldwide for myeloma at diagnosis, of whom 2309 had cytogenetic studies and 5387 had analyses by ?uorescent in situ hybridization (iFISH). […]

Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group

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Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classi?ed as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with different cytogenetic and molecular ?ndings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (X20%) and absolute number (X2 x 109/l) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be re-examined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy […]

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. […]

Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib

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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 relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T(0)). The median age at diagnosis was 58 years, and time from diagnosis to T(0) was 3.3 years. Following T(0), 213 […]

IMWG consensus on maintenance therapy in multiple myeloma

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Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/event-free survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomidemaintenance treatment after autologous stem cell transplantation and one […]

IMWG Consensus Statement Regarding the Current Status of Allogeneic Stem Cell Transplantation for Multiple Myeloma

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There has been much controversy in over two decades about the role of allogeneic stem cell transplant in myeloma. Early studies conducted in Europe and at the Fred Hutchinson Cancer Center in Seattle, WA, consistently demonstrated high treatment-related mortality (TRM) of approximately 45% in heavily patients receiving full myeloablative allogeneic transplant (full allo). Overall survival rates in these studies were generally less than 30% at five years. Full allo in myeloma patients was therefore largely abandoned worldwide in the early 1990s. There were, however, some long-term remission durations among patients treated within one year of diagnosis, after a single line of therapy, and with chemotherapy-sensitive disease. In fact, there was […]

International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation

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The role of high-dose therapy followed by autologous stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM) continues to evolve in the novel agent era. The choice of induction therapy has moved from conventional chemotherapy to newer regimens incorporating the immunomodulatory derivatives thalidomide or lenalidomide and the proteasome inhibitor bortezomib. These drugs combine well with traditional therapies and with one another to form various doublet, triplet, and quadruplet regimens. Up-front use of these induction treatments, in particular 3-drug combinations, has affected unprecedented rates of complete response that rival those previously seen with conventional chemotherapy and subsequent ASCT. Autotransplantation applied after novel-agent-based induction regimens provides further improvement in the […]

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