Multiple Myeloma

Description

• Multiple myeloma (MM) is a malignant proliferation of a single clone of plasma cells. These malignant cells produce monoclonal protein (immunoglobulin [Ig]) that can be detected in the blood and/or urine as it is filtered in the kidneys.
• MM is characterized by bony lytic lesions, hypercalcemia, increased susceptibility to infections, and renal impairment.
• Monoclonal gammopathy of undetermined significance (MGUS) is a common disorder with limited monoclonal plasma cell proliferation that can progress to smoldering MM (SMM) or symptomatic MM at rate of ~1% per year.

Epidemiology

• MM affects the older adults with a median age of 65 to 74 years.
• Accounts for nearly 2% of all cancers and 17% of hematologic malignancies in the United States
• African Americans about 2 to 3 times more commonly affected than Caucasians; less common in Asians

Incidence
7 cases per 100,000 in the United States annually

Prevalence
In 2018, there were ~160,000 recognized cases worldwide.

Etiology and Pathophysiology

• It is most likely caused by genetic alteration involving chromosomal abnormalities and sporadic mutations.
• Genetic damage in developing B lymphocytes occur at time of isotype switching.
• Chromosomal abnormalities involve Ig heavy chain translocations, with cyclin D1 t(11;14) the most common, and deletion of 17p13 (p53 locus).

Genetics
MM rarely occurs in familial clusters. A rare form of paratarg-7 protein might have pathogenic role.

Risk Factors

• Most cases have no known risks associated.
• Old age; immunosuppression; and exposure to chemicals, heavy metals, and ionizing radiation increase the risk of MM.

Commonly Associated Conditions

Secondary amyloidosis can be associated with MM and polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS).