The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network
Niels W.C.J. van de Donk,
Antonio Palumbo,
Hans Erik Johnsen,
Monika Engelhardt,
Francesca Gay,
Henrik Gregersen,
Roman Hajek,
Martina Kleber,
Heinz Ludwig,
Gareth Morgan,
Pellegrino Musto,
Torben Plesner,
Orhan Sezer,
Evangelos Terpos,
Anders Waage,
Sonja Zweegman,
Hermann Einsele,
Pieter Sonneveld,
Henk M. Lokhorst
Affiliations
Niels W.C.J. van de Donk
Department of Hematology, University Medical Center Utrecht, The Netherlands
Antonio Palumbo
Divisione di Ematologia dell’Università di Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin, Italy
Hans Erik Johnsen
Department of Hematology, Aalborg University Hospital, Aalborg, Denmark
Monika Engelhardt
Department of Hematology and Oncology, University of Freiburg Medical Center, Germany
Francesca Gay
Divisione di Ematologia dell’Università di Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin, Italy
Henrik Gregersen
Department of Hematology, Aalborg University Hospital, Aalborg, Denmark
Roman Hajek
Department of Haemato-oncology, University Hospital Ostrava and Faculty of Medicine, Czech Republic
Martina Kleber
Department of Hematology and Oncology, University of Freiburg Medical Center, Germany
Heinz Ludwig
Department of Medicine I, Wilhelminenspital Wien, Austria
Gareth Morgan
Institute of Cancer Research, Royal Marsden Hospital, London, UK
Pellegrino Musto
Scientific Direction, Centro di Riferimento Oncologico della Basilicata, Istituto di Ricovero e Cura a Carattere Scientifico, Rionero in Vulture, Italy
Torben Plesner
Department of hematology at Vejle Hospital, Denmark
Orhan Sezer
Department of Hematology, Memorial Hospital, Istanbul, Turkey
Evangelos Terpos
Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Greece
Anders Waage
Department of Hematology, St. Olavs Hospital, Norwegian University of Science and Technology, Trondheim, Norway
Sonja Zweegman
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands
Hermann Einsele
Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany
Pieter Sonneveld
Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands
Henk M. Lokhorst
Department of Hematology, University Medical Center Utrecht, The Netherlands
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 Waldenström’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.
