Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group

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The International Myeloma Working Group consensus updates the definition for high-risk (HR) multiple myeloma based on cytogenetics Several cytogenetic abnormalities such as t(4;14), del(17/17p), t(14;16), t(14;20), nonhyperdiploidy, and gain(1q) were identified that confer poor prognosis. The prognosis of patients showing these abnormalities may vary with the choice of therapy. Treatment strategies have shown promise for HR cytogenetic diseases, such as proteasome inhibition in combination with lenalidomide/pomalidomide, double autologous stem cell transplant plus bortezomib, or combination of immunotherapy with lenalidomide or pomalidomide. Careful analysis of cytogenetic subgroups in trials comparing different treatments remains an important goal. Cross-trial comparisons may provide insight into the effect of new drugs in patients with cytogenetic […]

International Myeloma Working Group recommendations for global myeloma care

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Recent developments have led to remarkable improvements in the assessment and treatment of patients with multiple myeloma (MM). New technologies have become available to precisely evaluate the biology and extent of the disease, including information about cytogenetics and genetic abnormalities, extramedullary manifestations and minimal residual disease. New, more effective drugs have been introduced into clinical practice, which enable clinicians to significantly improve the outcome of patients but also pose new challenges for the prevention and management of their specific side effects. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of patients, as access to the most sophisticated advances may […]

New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG)

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Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data […]

International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation

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PURPOSE: To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation. METHODS: A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized. RESULTS: Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, […]

Management of multiple myeloma in Asia: resource-stratified guidelines

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Treatment of multiple myeloma has undergone substantial developments in the past 10 years. The introduction of novel drugs has changed the treatment of the disease and substantially improved survival outcomes. Clinical practice guidelines based on evidence have been developed to provide recommendations on standard treatment approaches. However, the guidelines do not take into account resource limitations encountered by developing countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs in Asian countries hinder the delivery of optimum care to every patient with multiple myeloma in Asia. In this Review we outline the guidelines that correspond with different levels of health-care resources and expertise, with the aim to […]

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 […]

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 […]

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

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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. […]

IMWG Guidelines for Facilities and Services for the Management of Myeloma Patients

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The following guidelines are excerpted from Palumbo et al, International Myeloma Working Group Guidelines for the Management of Multiple Myeloma Patients Ineligible for Standard High-Dose Chemotherapy with Autologous Stem Cell Transplantation, Leukemia (2009), 1-15. The most important feature of any clinical unit established to care for myeloma patients is the training and expertise of the medical staff.   Below are the diagnostic and specialty services required to support treatment decision-making and patient management.  Patient support services, though desirable hallmarks of a good specialty center, are not absolutely essential. Facilities It is recommended that a special clinical unit be developed devoted to the treatment of MM, with clear policies and protocols for […]

Genetic polymorphisms of EPHX1, Gsk3beta, TNFSF8 and myeloma cell DKK-1 expression linked to bone disease in myeloma

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Bone disease in myeloma occurs as a result of complex interactions between myeloma cells and the bone marrow microenvironment. A custom-built DNA single nucleotide polymorphism (SNP) chip containing 3404 SNPs was used to test genomic DNA from myeloma patients classified by the extent of bone disease. Correlations identified with a Total Therapy 2 (TT2) (Arkansas) data set were validated with Eastern Cooperative Oncology Group (ECOG) and Southwest Oncology Group (SWOG) data sets. Univariate correlates with bone disease included: EPHX1, IGF1R, IL-4 and Gsk3beta. SNP signatures were linked to the number of bone lesions, log(2) DKK-1 myeloma cell expression levels and patient survival. Using stepwise multivariate regression analysis, the following SNPs: […]