title: Second primary malignancies in multiple myeloma: an overview and IMWG consensus.
abstract: 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.
  
  
  
  A Panel of International Myeloma Working Group members reviewed the most relevant data published in the literature as full papers, or presented at meetings of the American Society of Clinical Oncology, American Society of Hematology, European Hematology Association, or International Myeloma Workshops, up to June 2016. Here, we present the recommendations of the Panel, based on this literature review.
  
  
  
  Overall, the risk of SPMs in MM is low, multifactorial, and partially related to the length of patients' survival and MM intrinsic susceptibility. Studies suggest a significantly increased incidence of SPMs when lenalidomide is administered either following, or concurrently with, oral melphalan. Increased SPM incidence has also been reported with lenalidomide maintenance following high-dose melphalan, albeit to a lesser degree. In both cases, the risk of death from MM was significantly higher than the risk of death from SPMs, with lenalidomide possibly providing a survival benefit. No increase in SPM incidence was reported with lenalidomide plus dexamethasone (without melphalan), or with bortezomib plus oral melphalan, dexamethasone, or thalidomide.
  
  
  
  In general, the risk of SPMs should not alter the current therapeutic decision-making process in MM. However, regimens such as lenalidomide plus dexamethasone should be preferred to prolonged exposure to lenalidomide plus oral melphalan. SPM risk should be carefully discussed with the patient in the context of benefits and risks of different treatment options.
authors.affiliation: Scientific Direction, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Musto
authors.affiliation: Hematologic Oncology, Dana-Farber Cancer Institute, Boston, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: Hematology, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Attal
authors.affiliation: Hematologic Oncology, Dana-Farber Cancer Institute, Boston, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Richardson
authors.affiliation: School of Medicine, University of Maryland, Baltimore, USA.
authors.forename: A
authors.initials: A
authors.lastname: Badros
authors.affiliation: Department of Hematology, Myeloma and Lymphoma Center, Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Hou
authors.affiliation: Hematology/Oncology, Tufts Medical Center, Boston.
authors.forename: R
authors.initials: R
authors.lastname: Comenzo
authors.affiliation: Department of Hematology, Myeloma and Lymphoma Center, Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.affiliation: Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, USA.
authors.forename: B G M
authors.initials: BGM
authors.lastname: Durie
authors.affiliation: Navarra University Clinic, CIMA, Pamplona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: San Miguel
authors.affiliation: Internal Medicine II, University Hospital Wuerzburg, Wuerzburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: W M
authors.initials: WM
authors.lastname: Chen
authors.affiliation: Hematology Clinic, Hôpital Saint Antoine, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Garderet
authors.affiliation: Unit of Hematology and Stem Cell Transplantation, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pietrantuono
authors.affiliation: Department of Hematology and Oncology, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hillengass
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Kyle
authors.affiliation: Hematology, University Hospital, Nantes, France.
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Spanish Myeloma Group, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Hematologic Oncology, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: O
authors.initials: O
authors.lastname: Landgren
authors.affiliation: 1st Medical Department and Oncology, Wilhelminenspital Der Stat Wien, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Ludwig
authors.affiliation: Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Larocca
authors.affiliation: School of Medicine, University of California, San Francisco, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mahindra
authors.affiliation: Department of Specialized, Experimental, & Diagnostic Medicine, University of Bolgona, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cavo
authors.affiliation: Medical Oncology, NYU Comprehensive Cancer Center, New York.
authors.forename: A
authors.initials: A
authors.lastname: Mazumder
authors.affiliation: Department of Medicine, Roswell Park Cancer Center, Buffalo, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: McCarthy
authors.affiliation: Department of Hematology, Hospital Universitario Rutz y Paez, Bolivar, Venezuela.
authors.forename: A
authors.initials: A
authors.lastname: Nouel
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Rajkumar
authors.affiliation: Department of Oncology, Saint John Regional Hospital, Saint John, New Brunswick, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Reiman
authors.affiliation: Hematology Department, Hospital de Clinicas, Montevideo, Uruguay.
authors.forename: E
authors.initials: E
authors.lastname: Riva
authors.affiliation: Hematology Department, Memorial Hospital, Istanbul, Turkey.
authors.forename: O
authors.initials: O
authors.lastname: Sezer
authors.affiliation: School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Terpos
authors.affiliation: Department of Hematology and Coagulation Disorders, Skane University Hospital, Malmo, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Turesson
authors.affiliation: Levine Cancer Institute, Carolinas Healthcare System, Charlotte.
authors.forename: S
authors.initials: S
authors.lastname: Usmani
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Weiss
authors.affiliation: Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D006801:Humans; D015994:Incidence; D009101:Multiple Myeloma / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000209:etiology*; D012307:Risk Factors
keywords: International Myeloma Working Group; SPM; lenalidomide; multiple myeloma; risk factors; second primary malignancy