title: Smoldering multiple myeloma requiring treatment: time for a new definition?
abstract: Smoldering multiple myeloma (SMM) bridges the gap between monoclonal gammopathy of undetermined significance (a mostly premalignant disorder) and active multiple myeloma (MM). Until recently, no interventional study in patients with SMM showed improved overall survival (OS) with therapy as compared with observation. A report from the PETHEMA-GEM (Programa Español de Tratamientos en Hematologica) group described both fewer myeloma-related events and better OS among patients with high-risk SMM who were treated with lenalidomide and dexamethasone. This unique study prompted us to review current knowledge about SMM and address the following questions: (1) Are there patients currently defined as SMM who should be treated routinely? (2) Should the definitions of SMM and MM be reconsidered? (3) Has the time come when not treating is more dangerous than treating? (4) Could unintended medical harm result from overzealous intervention? Our conclusion is that those patients with the highest-risk SMM (extreme bone marrow plasmacytosis, extremely abnormal serum immunoglobulin free light chain ratio, and multiple bone lesions detected only by modern imaging) should be reclassified as active MM so that they can receive MM-appropriate therapy and the paradigm of careful observation for patients with SMM can be preserved.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN;
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.forename: Asher
authors.initials: A
authors.lastname: Chanan-Khan
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Prashant
authors.initials: P
authors.lastname: Kapoor
authors.forename: P Leif
authors.initials: PL
authors.lastname: Bergsagel
authors.forename: Arleigh
authors.initials: A
authors.lastname: McCurdy
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: John A
authors.initials: JA
authors.lastname: Lust
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Steven R
authors.initials: SR
authors.lastname: Zeldenrust
authors.forename: Craig
authors.initials: C
authors.lastname: Reeder
authors.forename: Vivek
authors.initials: V
authors.lastname: Roy
authors.forename: Francis
authors.initials: F
authors.lastname: Buadi
authors.forename: David
authors.initials: D
authors.lastname: Dingli
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Hayman
authors.forename: Nelson
authors.initials: N
authors.lastname: Leung
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Joseph
authors.initials: J
authors.lastname: Mikhael
authors.forename: Shaji K
authors.initials: SK
authors.lastname: Kumar
mesh_terms: D018450:Disease Progression; D006801:Humans; D010265:Paraproteinemias / Q000145:classification* / Q000175:diagnosis; D017285:Polymyositis / Q000145:classification* / Q000175:diagnosis* / Q000401:mortality; D011230:Precancerous Conditions / Q000145:classification* / Q000175:diagnosis; D012307:Risk Factors; D009626:Terminology as Topic