Multiple myeloma is a plasma cell neoplasm and the second most common hematologic malignancy in the United States, although overall incidence rates are relatively low at approximately 32,000 annually. The overall five-year survival rate is 52%, and most people are diagnosed with the disease in later stages.

One of the biggest risk factors is age: most diagnoses are in people older than 60 years, and incidence is less than 2% in those younger than 40. It is more common in men and non-Hispanic blacks. A family history of myeloma or other plasma cell diseases also seem to increase a person’s risk.

Monoclonal gammopathy of unknown significance (commonly known as MGUS) is the presence of an abnormal monoclonal protein in the blood and can be a precursor for the disease.

Presentation and Diagnosis

Patients may present with several signs and symptoms or may be asymptomatic with evidence of incidental laboratory findings. Anemia can cause fatigue, shortness of breath, and pallor. Other blood count abnormalities such as leukopenia and thrombocytopenia may be found. Hypercalcemia can result from bone breakdown and presents as renal insufficiency and proteinuria. Bone pain can be a presenting symptom; obtain skeletal imaging for lytic bone lesions. Detecting the level of plasma cells in bone marrow biopsy helps to determine the extent of disease.

Diagnostic Biomarkers

Established biomarkers in the revised international staging system include beta-2 microglobulin, serum albumin, lactate dehydrogenase, and chromosomal abnormalities. Additionally, the Durie-Salmon Staging System uses quantitative immunoglobulins as a key biomarker. Serum and urinary analyses will help detect and quantify the specific monoclonal protein. Serum creatinine assesses the impact on kidney function.

High-risk chromosomal abnormalities include deletion of chromosome 17 del(17p) and rearrangement of the immunoglobulin heavy chain gene on chromosome 14. Chromosome 1 is often altered as well, and the National Comprehensive Cancer Network recommends that, at minimum, cytogenetics at diagnosis should include 17p13 deletions, 4;14 and 14;16 translocations, and chromosome 1 amplification.

Because multiple myeloma is a heterogeneous disease, novel biomarkers may be useful in further specification and risk stratification.


Multiple myeloma is usually not curable unless it presents as a solitary plasmacytoma. However, treatment advancements, including several newer monoclonal antibodies, immunomodulatory drugs, and proteasome inhibitors, have steadily improved survival rates during the past 10 years. Other therapies such CAR T-cell therapy are being studied. Some patients with asymptomatic smoldering myeloma may not require immediate treatment and can be followed by watchful waiting. As renal dysfunction, hypercalcemia, or anemia worsens or lytic bone lesions develop, active treatment is initiated.

A patient’s performance status and disease aggressiveness determine treatment options. Patients will often receive a triplet therapy involving a proteasome inhibitor like bortezomib, a steroid like dexamethasone, and an immunomodulatory agent such as lenalidomide. Alternatively, chemotherapy (bortezomib plus dexamethasone) may be recommended. Some patients may receive a monoclonal antibody to CD38 such as daratumumab with or without doublet therapy for relapsed or refractory multiple myeloma.

Patients will continue these cycles with interval monitoring of the monoclonal protein, immunoglobulins, light chains, or other markers of improvement. Maintenance therapy with lenalidomide alone or lenalidomide plus bortezomib is sometimes used.

Other approaches include single or tandem autologous stem cell transplantation or allogeneic stem cell transplantation. Radiation therapy can be used for boney disease and may improve pain.

Side Effects and Supportive Care

Supportive care involves use of growth factors and erythropoietin as needed, transfusion support, and infection prevention. Bisphosphonates like pamidronate and zoledronate are often used to reduce bone-related complications and pain. Antivirals may be given for herpes prevention, particularly in those treated with a proteasome inhibitor or daratumumab. Peripheral neuropathy is a common side effect from bortezomib that may require dose attenuation, holding of therapy, or pharmacologic or nonpharmacologic treatment such as gabapentin. Venous thrombosis risk is increased, especially with therapies such lenalidomide and steroids, and prophylaxis is recommended.

Supportive care can reduce symptoms and improve quality of life. Patients who experience advanced and refractory disease should have advanced care planning and palliative care established early on to improved quality of life.

Provide patients and caregivers with ongoing psychosocial evaluation and support, and regularly review healthy living and wellness strategies. Patients may live many years with multiple myeloma but may need to manage multiple comorbidities because of the disease and treatment. Ongoing survivorship care should be discussed.