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Second primary malignancies in multiple myeloma: an overview and IMWG consensus

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Therapeutic advancements following the introduction of autologous stem cell transplantation and ‘novel’ agents have significantly improved clinical outcomes for patients with multiple myeloma (MM). Increased life expectancy, however, has led to renewed concerns about the long-term risk of second primary malignancies (SPMs). This review outlines the most up-to-date knowledge of possible host-, disease-, and treatment-related risk factors for the development of SPMs in patients with MM, and provides practical recommendations to assist physicians. Authors: P. Musto  K. C. Anderson  M. Attal  P. G. Richardson  A. Badros  J. Hou  R. Comenzo J. Du  B. G. M. Durie  J. San Miguel  H. Einsele  W. M. Chen  L. Garderet  G. Pietrantuono J. Hillengass […]

International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma

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Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow […]

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 the Diagnosis and Management of Myeloma-Related Renal Impairment

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Recommendations developed by the International Myeloma Working Group (IMWG), the research arm of the IMF, were published online in the Journal of Clinical Oncology on March 14, 2016. The recommendations are based on data gathered through December 2015 and analyzed by Meletios A. Dimopoulos, MD, from the University of Athens in Greece, and colleagues.

Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group

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The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and […]

Gene signature combinations improve prognostic stratification of multiple myeloma patients

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Multiple myeloma (MM) is a plasma cell neoplasm with significant molecular heterogeneity. Gene expression profiling (GEP) has contributed significantly to our understanding of the underlying biology and has led to several prognostic gene signatures. However, the best way to apply these GEP signatures in clinical practice is unclear. In this study, we investigated the integration of proven prognostic signatures for improved patient risk stratification. Three publicly available MM GEP data sets that encompass newly diagnosed as well as relapsed patients were analyzed using standardized estimation of nine prognostic MM signature indices and simulations of signature index combinations. Cox regression analysis was used to assess the performance of simulated combination indices. Taking the average of multiple GEP signature indices was a simple but highly effective way of integrating multiple GEP signatures. Furthermore, although adding more signatures in general improved performance substantially, we identified a core signature combination, EMC92+HZDCD, as the top-performing prognostic signature combination across all data sets. In this study, we provided a rationale for gene signature integration and a practical strategy to choose an optimal risk score estimation in the presence of multiple prognostic signatures.

International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple Myeloma

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The updated criteria for the diagnosis of myeloma represent a paradigm shift in the approach to myeloma and have considerable impact on the management of the disease. For decades the diagnosis of multiple myeloma required the presence of end-organ damage known as the CRAB criteria, including increased calcium level, renal dysfunction, anemia, and destructive bone lesions. The updated criteria allow for treatment of patients who are at such high risk of progression to symptomatic disease that it is clear they would benefit from therapy—and also potentially live longer—if they were treated before serious organ damage occurred. The revised IMWG criteria allow, in addition to the classic CRAB features, three “myeloma defining […]

Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma

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In contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop a collaborative initiative to move the research agenda forward.

Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group

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The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Authors: Antonio Palumbo, Hervé Avet-Loiseau, Stefania Oliva, Henk M. Lokhorst, Hartmut Goldschmidt, Laura Rosinol, Paul Richardson, Simona Caltagirone, Juan José Lahuerta, Thierry Facon, Sara Bringhen, Francesca Gay, Michel Attal, Roberto Passera, Andrew Spencer, Massimo Offidani, Shaji Kumar, Pellegrino Musto, Sagar Lonial, Maria T. Petrucci, Robert Z. Orlowski, Elena Zamagni, Gareth Morgan, […]

Geriatric assessment predicts survival and toxicities in elderly myeloma: an International Myeloma Working Group report

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The IMF’s research arm, the International Myeloma Working Group (IMWG), published an important new study on the assessment of elderly myeloma patients in the journal Blood. In the paper, the IMWG introduces a scoring system developed to classify the frailty of elderly patients. The international study, which analyzed data from more than 850 newly diagnosed patients, found that the IMWG frailty score predicted mortality and the risk of toxicity in elderly myeloma patients. The frailty score could be a helpful tool in better assessing patients and providing them with more suitable therapies. Authors: Antonio Palumbo, Sara Bringhen, Maria-Victoria Mateos, Alessandra Larocca, Thierry Facon, Shaji K. Kumar, Massimo Offidani, Philip McCarthy, […]