title: The Changing Landscape of Smoldering Multiple Myeloma: A European Perspective.
abstract: Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammopathy of undetermined significance to multiple myeloma (MM), based on higher levels of circulating monoclonal immunoglobulin and bone marrow plasmocytosis without end-organ damage. Until a Spanish study reported fewer MM-related events and better overall survival among patients with high-risk SMM treated with lenalidomide and dexamethasone, prior studies had failed to show improved survival with earlier intervention, although a reduction in skeletal-related events (without any impact on disease progression) has been described with bisphosphonate use. Risk factors have now been defined, and a subset of ultra-high-risk patients have been reclassified by the International Myeloma Working Group as MM, and thus will require optimal MM treatment, based on biomarkers that identify patients with a >80% risk of progression. The number of these redefined patients is small (∼10%), but important to unravel, because their risk of progression to overt MM is substantial (≥80% within 2 years). Patients with a high-risk cytogenetic profile are not yet considered for early treatment, because groups are heterogeneous and risk factors other than cytogenetics are deemed to weight higher. Because patients with ultra-high-risk SMM are now considered as MM and may be treated as such, concerns exist that earlier therapy may increase the risk of selecting resistant clones and induce side effects and costs. Therefore, an even more accurate identification of patients who would benefit from interventions needs to be performed, and clinical judgment and careful discussion of pros and cons of treatment initiation need to be undertaken. For the majority of SMM patients, the standard of care remains observation until development of symptomatic MM occurs, encouraging participation in ongoing and upcoming SMM/early MM clinical trials, as well as consideration of bisphosphonate use in patients with early bone loss.
authors.affiliation: Department of Hematology, University Hospital of Liège, Liège, Belgium jo.caers@chu.ulg.ac.be.
authors.forename: Jo
authors.initials: J
authors.lastname: Caers
authors.affiliation: Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clínic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández de Larrea
authors.affiliation: Hopital La Miletrie, CHU Poitiers, Poitiers, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.affiliation: Hematology Laboratory, Groupe Interdisciplinaire de Génoprotéomique Appliquée-I3, University of Liège, Liège, Belgium.
authors.forename: Roy
authors.initials: R
authors.lastname: Heusschen
authors.affiliation: Department of Medicine I, Wilhelminen Hospital, Vienna, Austria.
authors.forename: Niklas
authors.initials: N
authors.lastname: Zojer
authors.affiliation: Internal Medicine Department, Rennes University Hospitals, Hôpital Sud, Rennes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Decaux
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: Department of Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Minnema
authors.affiliation: Department of Hematology Jagiellonian University, Cracow, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Jurczyszyn
authors.affiliation: Department of Hematology, University Hospital of Liège, Liège, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Beguin
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Wäsch
authors.affiliation: Myeloma Unit, Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
authors.forename: Meletios
authors.initials: M
authors.lastname: Dimopoulos
authors.affiliation: Instituto de Investigación Biomédica de Salamanca-Hematology, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Department of Medicine I, Wilhelminen Hospital, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Engelhardt
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D003907:Dexamethasone / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D018450:Disease Progression; D005060:Europe; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D009194:Myeloma Proteins / Q000032:analysis; D012307:Risk Factors; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004164:Diphosphonates; D007147:Immunoglobulin Light Chains; D009194:Myeloma Proteins; C085016:multiple myeloma M-proteins; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide
keywords: Progression; Risk factors; Smoldering multiple myeloma; Treatment