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

Posted · Add Comment

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

Posted · Add Comment

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 […]

International Myeloma Working Group (IMWG) Guidelines for Serum Free Light Chain Analysis in Multiple Myeloma and Related Disorders

Posted · Add Comment

For the more than 3% of myeloma patients who have non-secretory or oligosecretory disease, and for the majority of patients with AL amyloidosis (AL), the traditional methods of measuring circulating monoclonal immunoglobulins (electrophoresis, immunoelectrophoresis, immunofixation electrophoresis, and nephelometric measurement of immunoglobulin heavy chains of serum) are not adequate. The development of an assay that measures serum immunoglobulin-free light chains has demonstrated utility for monitoring these patients and for other specific indications, such as monitoring heavily-pretreated patients at relapse. The following guidelines from the International Myeloma Working Group describe the potential uses of the serum free light chain (SFLC) assay and distinguish which uses have proved their utility and which are […]

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

Posted · Add Comment

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 […]

Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering (Asymptomatic) Multiple Myeloma: IMWG Consensus Perspectives Risk Factors for Progression and Guidelines for Monitoring and Management

Posted · Add Comment

Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21,463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom’s macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low- risk MGUS is characterized by having an M protein < 15 g/L, IgG type and a normal free light chain (FLC) ratio. Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every two to three years or when symptoms suggestive of a plasma cell malignancy arise. Patients with intermediate and high-risk MGUS should be followed in six months […]

International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma

Posted · Add Comment

The International Myeloma Working Group established the below criteria in order to: facilitate precise comparisons of efficacy between new treatment strategies in trials incorporate the serum free light chain (FLC) assay to include assessment of patients with oligo-secretory and non-secretory disease provide stricter definitions for CR (complete response) provide classifications that would improve detail and correct inconsistencies in prior response criteria. The following criteria reconcile various previously used systems for assessing response and have been universally adopted. Response IMWG criteria sCR CR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow3 by immunohistochemistry or immunofluorescence4 CR Negative immunofixation on the serum and urine and […]

IMWG Guidelines on Imaging Techniques in the Diagnosis and Monitoring of Multiple Myeloma

Posted · Add Comment

Up to 90% of myeloma patients develop osteolytic lesions, a major cause of morbidity and mortality, during the course of their disease. 2  Appropriate use of imaging techniques is essential to identify and characterize skeletal complications resulting from MM, to determine the extent of intramedullary and extramedullary foci, and to evaluate disease progression. Several imaging techniques are used to clarify bone and soft tissue disease in the diagnosis and management of myeloma: conventional radiography, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine imaging. The following International Myeloma Working Group (IMWG) guidelines provide recommendations for the use of each of the technologies. The appropriate use of these various technologies […]

International Myeloma Working Group molecular classification of multiple myeloma: spotlight review

Posted · Add Comment

Myeloma is a malignant proliferation of monoclonal plasma cells. Although morphologically similar, several subtypes of the disease have been identified at the genetic and molecular level. These genetic subtypes are associated with unique clinico- pathological features and dissimilar outcome. At the top hierarchical level, myeloma can be divided into hyperdiploid and non-hyperdiploid subtypes. The latter is mainly composed of cases harboring IgH translocations, generally associated with more aggressive clinical features and shorter survival. The three main IgH translocations in myeloma are the t(11;14)(q13;q32), t(4;14)(p16;q32) and t(14;16)(q32;q23). Trisomies and a more indolent form of the disease characterize hyperdiploid myeloma. A number of genetic progression factors have been identified including deletions of […]

International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma

Posted · Add Comment

Several imaging technologies are used for the diagnosis and management of patients with multiple myeloma (MM). Conventional radiography, computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine imaging are all used in an attempt to better clarify the extent of bone disease and soft tissue disease in MM. This review summarizes all available data in the literature and provides recommendations for the use of each of the technologies. Conventional radiography still remains the ‘gold standard’ of the staging procedure of newly diagnosed and relapsedmyeloma patients. MRI gives information complementary to skeletal survey and is recommended in MM patients with normal conventional radiography and in all patients with an apparently […]

Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping

Posted · Add Comment

A venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism is a major concern in the treatment of patients with multiple myeloma with thalidomide. The susceptibility to developing a VTE in response to thalidomide therapy is likely to be influenced by both genetic and environmental factors. To test genetic variation associated with treatment related VTE in patient peripheral blood DNA, we used a custom-built molecular inversion probe (MIP)-based single nucleotide polymorphism (SNP) chip containing 3404 SNPs. SNPs on the chip were selected in “functional regions” within 964 genes spanning 67 molecular pathways thought to be involved in the pathogenesis, treatment response, and side effects associated with myeloma therapy. Patients […]