title: Multiple myeloma and its therapies: to what extent do they contribute to the increased incidence of second malignant neoplasms?
abstract: BACKGROUND
  The high risk of another cancer once one has been diagnosed is well known. Furthermore, a clear association exists between the use of some cytotoxic agents and chemotherapy-induced malignancies.
  
  
  METHODS
  This review is set to explore the relationship between multiple myeloma, its modern therapies and the development of second cancers due to various genetic, immune, and environmental (including iatrogenic) factors. Most relevant publications were identified through the PubMed database and by reviewing the drug information released by the US Federal Drug Administration.
  
  
  RESULTS
  Our comprehensive analysis identified several retrospective population studies, cohort group analyses and a number of case reports linking myeloma with other cancers in the world literature. A majority of these studies suggest that incidence of second solid and hematologic malignancies is significantly increased in patients with multiple myeloma and its precursor lesion, monoclonal gammopathy of unknown significance. In addition, incidence of second malignancies has been found increased in the family members of these individuals, especially in their first-degree relatives.
  
  
  CONCLUSIONS
  Analysis of the existing literature cohorts does not discriminate between the burden of second cancers in treated myeloma patients as opposed to the patients followed with the wait-and-watch approach. Notably, the rate of second malignant neoplasms in multiple myeloma may be further increased by certain myeloma therapies. These cancers include, for the most part, hematologic malignancies such as acute leukemias and certain lymphomas. While there is no question about the role of alkylating agents and topoisomerase II inhibitors in this regard, further research is necessary to determine whether the excess of second cancers represents a direct consequence of lenalidomide use.
authors.affiliation: Medical Oncology and Blood Disorders, Gothic Park, Hartford, CT 06105, USA. c_dasanu@yahoo.com
authors.forename: Constantin A
authors.initials: CA
authors.lastname: Dasanu
authors.forename: Prerna
authors.initials: P
authors.lastname: Mewawalla
authors.forename: Joanna
authors.initials: J
authors.lastname: Grabska
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000453:epidemiology; D004777:Environment; D005260:Female; D019337:Hematologic Neoplasms / Q000453:epidemiology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology; D009101:Multiple Myeloma / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D010051:Ovarian Neoplasms / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000453:epidemiology; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents