Epidemiology, Staging, and Management of Multiple Myeloma

Abstract

Multiple myeloma (MM) is a plasma cell disorder that is on the rise throughout the world, especially in the US, Australia, and Western Europe. In the US, MM accounts for almost 2% of cancer diagnoses and over 2% of cancer deaths (more than double the global proportion). Incidence has risen by 126% globally and over 40% in the US since 1990, while global mortality has risen by 94% and US mortality has fallen by 18%. The 5 year survival in the US has more than doubled over the past decades with the introduction of new targeted therapies and transplant techniques. Risk factors for MM include age (average age of diagnosis is 69), race (African Americans are over double as likely to be diagnosed), sex (men are at a 1.5× risk), and family history. Diagnosis includes serum or urine electrophoresis and free light-chain assay but requires bone marrow biopsy. It is distinguished from smoldering myeloma and monoclonal gammopathy of undetermined significance by a high (>3 g/dL) level of M-protein (monoclonal light chains) and the presence of CRAB (Hypercalcemia, Renal failure, Anemia, Bone pain) symptoms, which include hypercalcemia, renal failure, anemia, and bone pain, suggesting an end-organ damage. International staging system staging involves beta 2 microglobulin and albumin levels, while the revised system considers prognostic factors such as lactate dehydrogenase levels and chromosomal abnormalities. Front-line management includes induction regimen, maintenance therapy and hematopoietic cell transplantation for eligible patients and bisphosphonates or bone-stimulating agents for the prevention of skeletal events. Treatment for relapsed disease includes newly approved monoclonal antibodies like the CD38-targeting daratumumab, proteasome inhibitors, immunomodulating agents, and investigational therapies such as B cell maturation antigen Chimeric antigen receptor T cells.

Keywords: diagnosis; epidemiology; etiology; incidence; mortality; multiple myeloma; risk factors; staging; treatment.

Figure 1

Map showing the estimated age-standardized incidence rates per 100,000 (world) in 2018 of multiple myeloma (MM) for both sexes and all ages. Created with mapchart.net. Data obtained from GLOBOCAN 2018 [7].

Figure 2

Map showing the estimated age-standardized mortality rates per 100,000 (world) in 2018 of multiple myeloma for both sexes and all ages. Created with mapchart.net. Data obtained from GLOBOCAN 2018 [7].

Figure 3

Graph showing the estimated cumulative risk of incidence in 2018 of multiple myeloma for both sexes, ages 0–74. Created with Tableau 2019.2. Data obtained from GLOBOCAN 2018 [7].

Figure 4

Graph showing the estimated number of prevalent cases (5 year) as a population in 2018 of multiple myeloma for both sexes, ages 0–74. Created with Tableau 2019.2 Data obtained from GLOBOCAN 2018 [7].

Figure 5

Bar chart showing the 5 year age-adjusted mortality rates from 2013–2017 by age for the United States. Created with Tableau 2019.2. Data source: SEER*Explorer [11].

Figure 6

Bar chart showing the United States’ 5-year age-adjusted mortality rates from 2013–2017 for all races (including Hispanics). Created with Tableau 2019.2. Data source: SEER*Explorer [11].

Figure 7

Modified flow chart depicting the general outline of treatment options for MM adopted from mSMART.org. HCT: hematopoietic stem cell transplantation.