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

Posted · Add Comment

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

Posted · Add Comment

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

Posted · Add Comment

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 […]

International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma

Posted · Add Comment

PURPOSE: To define consensus statement regarding allogeneic stem-cell transplantation (Allo-SCT) as a treatment option for multiple myeloma (MM) on behalf of International Myeloma Working Group. PATIENTS AND METHODS: In this review, results from prospective and retrospective studies of Allo-SCT in MM are summarized. RESULTS: Although the introduction of reduced-intensity conditioning (RIC) has lowered the high treatment-related mortality associated with myeloablative conditioning, convincing evidence is lacking that Allo-RIC improves the survival compared with autologous stem-cell transplantation. CONCLUSION: New strategies are necessary to make Allo-SCT safer and more effective for patients with MM. Until this is achieved, Allo-RIC in myeloma should only be recommended in the context of clinical trials. Authors: Lokhorst […]

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

Posted · Add Comment

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 patient’s individual risk factors. Risk factors for venous thromboembolism (VTE) in myeloma patients […]

IMWG consensus statement on the role of vertebral augmentation in multiple myeloma

Posted · Add Comment

Following are the recommendations of the IMWG on role of minimally invasive percutaneous injection of polymethyl methacrylate (PMMA), first developed as “vertebroplasty” in France in the late 1980s, as treatment for painful vertebral compression fractures (VCFs). Consequences of VCF-related kyphosis Compression of abdominal contents Anorexia, weight loss Decreased lung capacity Limited exercise tolerance/physical activity Anterior loading of spine Subsequent fractures Increasing kyphosis and deformity Types of vertebral augmentation Vertebroplasty: fractured bone fragments are stabilized and strengthened by percutaneous injection of PMMA. Kyphoplasty:  inflation of a balloon in the vertebral body prior to PMMA injection can restore vertebral height and reduce kyphotic deformity in addition to stabilizing the fractured vertebral body. […]