Blood Journal
Leading the way in experimental and clinical research in hematology

Second malignancies following multiple myeloma: from 1960s to 2010s

  1. Anish Thomas1,
  2. Sham Mailankody1,
  3. Neha Korde1,
  4. Sigurdur Y. Kristinsson2,
  5. Ingemar Turesson3, and
  6. Ola Landgren1,*
  1. 1 Multiple Myeloma Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States;
  2. 2 Department of Medicine, Karolinska University Hospital and Institutet, Stockholm, Sweden;
  3. 3 Division of Medicine, Skane University Hospital, Malmo, Sweden
  1. * Corresponding author; email: landgreo{at}


Based on small numbers, recent reports from three randomized trials have consistently demonstrated more hematologic malignancies in patients treated with lenalidomide as maintenance (vs. placebo). This fact has prompted concern and highlighted the association between multiple myeloma and second malignancies. Furthermore, an excess of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) following multiple myeloma has been known for over four decades. Most prior studies have been restricted due to small numbers of patients, inadequate follow-up, and limitations of ascertainment of second malignancies. Although the underlying biological mechanisms of AML/MDS after multiple myeloma are unknown, treatment-related factors are presumed to be responsible. Recently, an excess risk of AML/MDS was found among 5652 patients with IgG/IgA (but not IgM) monoclonal gammopathy of undetermined significance (MGUS), supporting a role for disease-related factors. Furthermore, there is evidence to suggest that polymorphisms in germline genes may contribute to a person's susceptibility to subsequent cancers, while the potential influence of environmental and behavioral factors remains poorly understood. This review discusses current knowledge regarding second malignancies following multiple myeloma and gives future directions for efforts designed to characterize underlying biological mechanisms, with the goal to maximize survival and minimize the risk for second malignancies for individual patients.

  • Submitted December 21, 2011.
  • Accepted January 20, 2012.