TY - JOUR A1 - van de Donk, Niels W. C. J. A1 - Palumbo, Antonio A1 - Johnsen, Hans Erik A1 - Engelhardt, Monika A1 - Gay, Francesca A1 - Gregersen, Henrik A1 - Hajek, Roman A1 - Kleber, Martina A1 - Ludwig, Heinz A1 - Morgan, Gareth A1 - Musto, Pellegrino A1 - Plesner, Torben A1 - Sezer, Orhan A1 - Terpos, Evangelos A1 - Waage, Anders A1 - Zweegman, Sonja A1 - Einsele, Hermann A1 - Sonneveld, Pieter A1 - Lokhorst, Henk M. T1 - The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network JF - Haematologica N2 - Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenstrom's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance. KW - multiparameter flow-cytometry KW - hematopoietic cell transplantation KW - smoldering multiple-myeloma KW - venous thromboembolic disease KW - bone-mineral density KW - population-based cohort KW - term-follow-up KW - marrow plasma cells KW - significance MGUS KW - malignant transformation Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116050 SN - 0390-6078 VL - 99 IS - 6 ER - TY - JOUR A1 - Engelhardt, Monika A1 - Terpos, Evangelos A1 - Kleber, Martina A1 - Gay, Francesca A1 - Wäsch, Ralph A1 - Morgan, Gareth A1 - Cavo, Michele A1 - van de Donk, Niels A1 - Beilhack, Andreas A1 - Bruno, Benedetto A1 - Johnsen, Hans Erik A1 - Hajek, Roman A1 - Driessen, Christoph A1 - Ludwig, Heinz A1 - Beksac, Meral A1 - Boccadoro, Mario A1 - Straka, Christian A1 - Brighen, Sara A1 - Gramatzki, Martin A1 - Larocca, Alessandra A1 - Lokhorst, Henk A1 - Magarotto, Valeria A1 - Morabito, Fortunato A1 - Dimopoulos, Meletios A. A1 - Einsele, Hermann A1 - Sonneveld, Pieter A1 - Palumbo, Antonio T1 - European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma JF - Haematologica N2 - Multiple myeloma management has undergone profound changes in the past thanks to advances in our understanding of the disease biology and improvements in treatment and supportive care approaches. This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence. All patients with symptomatic disease should undergo risk stratification to classify patients for International Staging System stage (level of evidence: 1A) and for cytogenetically defined high-versus standard-risk groups (2B). Novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients remains the standard of care (1A). Induction therapy should include a triple combination of bortezomib, with either adriamycin or thalidomide and dexamethasone (1A), or with cyclophosphamide and dexamethasone (2B). Currently, allogeneic stem cell transplantation may be considered for young patients with high-risk disease and preferably in the context of a clinical trial (2B). Thalidomide (1B) or lenalidomide (1A) maintenance increases progression-free survival and possibly overall survival (2B). Bortezomib-based regimens are a valuable consolidation option, especially for patients who failed excellent response after autologous stem cell transplantation (2A). Bortezomib-melphalan-prednisone or melphalan-prednisone-thalidomide are the standards of care for transplant-ineligible patients (1A). Melphalan-prednisone-lenalidomide with lenalidomide maintenance increases progression-free survival, but overall survival data are needed. New data from the phase III study (MM-020/IFM 07-01) of lenalidomide-low-dose dexamethasone reached its primary end point of a statistically significant improvement in progression-free survival as compared to melphalan-prednisone-thalidomide and provides further evidence for the efficacy of lenalidomide-low-dose dexamethasone in transplant-ineligible patients (2B). KW - undetermined significance MGUS KW - stem-cell transplantation KW - multiparameter flow-cytpmetry KW - bortezomib plus dxamethasone KW - monoclonal gammopathy KW - randomized phase-3 trial KW - elderly patients KW - thalidomide maintenance KW - cereblon expression KW - autologous transplantation Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117477 VL - 99 IS - 2 ER - TY - JOUR A1 - Terpos, Evangelos A1 - Kleber, Martina A1 - Engelhardt, Monika A1 - Zweegman, Sonja A1 - Gay, Francesca A1 - Kastritis, Efstathios A1 - van de Donk, Niels W. C. J. A1 - Bruno, Benedetto A1 - Sezer, Orhan A1 - Broijl, Annemiek A1 - Bringhen, Sara A1 - Beksac, Meral A1 - Larocca, Alessandra A1 - Hajek, Roman A1 - Musto, Pellegrino A1 - Johnsen, Hans Erik A1 - Morabito, Fortunato A1 - Ludwig, Heinz A1 - Cavo, Michele A1 - Einsele, Hermann A1 - Sonneveld, Pieter A1 - Dimopoulos, Meletios A. A1 - Palumbo, Antonio T1 - European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications JF - Haematologica N2 - The European Myeloma Network provides recommendations for the management of the most common complications of multiple myeloma. Whole body low-dose computed tomography is more sensitive than conventional radiography in depicting osteolytic disease and thus we recommend it as the novel standard for the detection of lytic lesions in myeloma (grade 1A). Myeloma patients with adequate renal function and bone disease at diagnosis should be treated with zoledronic acid or pamidronate (grade 1A). Symptomatic patients without lytic lesions on conventional radiography can be treated with zoledronic acid (grade 1B), but its advantage is not clear for patients with no bone involvement on computed tomography or magnetic resonance imaging. In asymptomatic myeloma, bisphosphonates are not recommended (grade 1A). Zoledronic acid should be given continuously, but it is not clear if patients who achieve at least a very good partial response benefit from its continuous use (grade 1B). Treatment with erythropoietic-stimulating agents may be initiated in patients with persistent symptomatic anemia (hemoglobin < 10g/dL) in whom other causes of anemia have been excluded (grade 1B). Erythropoietic agents should be stopped after 6-8 weeks if no adequate hemoglobin response is achieved. For renal impairment, bortezomib-based regimens are the current standard of care (grade 1A). For the management of treatment-induced peripheral neuropathy, drug modification is needed (grade 1C). Vaccination against influenza is recommended; vaccination against streptococcus pneumonia and hemophilus influenza is appropriate, but efficacy is not guaranteed due to suboptimal immune response (grade 1C). Prophylactic aciclovir (or valacyclovir) is recommended for patients receiving proteasome inhibitors, autologous or allogeneic transplantation (grade 1A). KW - bone-disease KW - stem-cell transplantation KW - acute kidney injury KW - erythropoiesis-stimulating agents KW - recombinant-human-erythropoietin KW - randomized controlled trial KW - group consensus statement KW - newly-diagnosed myeloma KW - zoledonic acid KW - enal impairment Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141913 VL - 100 IS - 10 SP - 1254 EP - 1266 ER -