Multiple myeloma natural history

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Shyam Patel [3]

Overview

If left untreated, most of patients with multiple myeloma may progress to develop fatigue, bone pain, and pallor. Common complications of multiple myeloma include anemia, renal failure, skeletal complications, and neurological complications. The prognosis of multiple myeloma is good with treatment while without treatment multiple myeloma will result in death with a median survival of 7 months. Multiple myeloma is associated with a 10 year survival rate of 3%. The presence of plasma cell leukemia or soft tissue plasmacytomas is associated with a particularly poor prognosis among patients with multiple myeloma. According to a report published by the National Cancer Institute there is a 43.25% chance of 5 year survival.

Natural History

• Most patients with multiple myeloma are initially asymptomatic. If left untreated, most of the patients with multiple myeloma will gradually develop fatigue, bone pain, and pallor.
• In as many as 30-40% cases the diagnosis may be incidental and is often diagnosed on routine blood screening.
• The natural history of plasmacytoma involves a risk of progression to active multiple myeloma. After a median follow-up of 58 months, 67% of patients will develop progression to multiple myeloma. Approximately 20% of patients will die from progression of disease.
• The median overall survival for newly diagnosed multiple myeloma ranges from 2 to 10 years.

Complications

Complications that can develop as a result of multiple myeloma are divided into hematologic complications and systemic complications:

Hematologic complications

Hematologic complications of multiple myeloma are due to the accumulation of excess numbers of abnormal plasma cells, which impairs normal hematopoiesis. This is referred to as myelophthisis, or the replacement of normal bone marrow by infiltrating tumor cells. This can result in complications such as anemia, thrombocytopenia, and leukopenia.

• Anemia: Impaired erythroid progenitor formation leads to decreased red blood cell production, which results in anemia. The anemia is usually normocytic (mean corpuscular volume of 80-100 femtoliters). Patients can experience signs and symptoms including fatigue, mucosal and conjunctival pallor, shortness of breath, and decreased exercise tolerance. Severe anemia can occur in patients who have concurrent renal dysfunction from multiple myeloma, as erythropoietin production is impaired in patients with renal complications. Patients may require red blood cell transfusion if the hemoglobin level is less than 7 g/dl or if severe symptomatic anemia develops. Complications from transfusion include HIV infection, hepatitis B infection, hepatitis C infection, pulmonary edema from volume overload, alloimmunization to red blood cell products, and hemosiderosis (iron overload state).
• Thrombocytopenia: Impaired megakaryocyte formation leads to decreased platelet production, which results in thrombocytopenia. Patients can experience signs and symptoms including mucosal bleeding, upper and lower gastrointestinal bleeding, bruising, petechiae, and ecchymoses. In rare cases, fatal hemorrhage can occur. Patients may require platelet transfusion if the platelet count is less than 10,000 cells per microliter, or less than 50,000 cells per microliter in the setting of bleeding diathesis.
• Leukopenia: Impaired granulocyte and lymphocyte progenitor formation leads to decreased mature white blood cell production, which results in leukopenia. Patients can experience signs and symptoms including localized infections (pneumonia, urinary tract infections, cellulitis, dental infections), fevers, chills, and sepsis. In rare cases, infection can be very severe and lead to severe sepsis. Patients may require treatment with antibiotics. Of note, although the plasma cell burden is increased in multiple myeloma, these plasma cells do not function in a normal manner, and the abnormal paraprotein production in multiple myeloma does not confer adequate humoral immunity. Thus, patient can have normal plasma cell counts but can be functionally immunosuppressed.

Systemic complications

Systemic complications of multiple myeloma are due to the effects of plasma cells on various non-hematologic organs, such as the kidneys, bones, and nervous system.

• Skeletal complications: Skeletal-related events are diverse and include asymptomatic lytic lesions, symptomatic lytic lesions, and pathologic fractures. Pathologic fractures in the appendicular skeleton (long bones) can result in functional impairment and impaired mobility. Pathologic fractures in the axial skeleton (vertebral column) can result in more serious complications. Spinal cord compression occurs if pathologic fractures occur in the vertebral column with impingement of bony fragments on the spinal cord. Symptoms include back pain, numbness, dysthesias, decreased deep tendon reflexes, and loss of bowel or bladder control. Spinal cord compression is an oncologic emergency and requires urgent neurosurgical decompression, radiation therapy, and administration of dexamethasone 10mg IV followed by 4mg PO every 6 hours to prevent further cord compromise.
• Hypercalcemia: In patients with multiple myeloma, calcium is frequently greater than 11 mg/dl. Hypercalcemia can result in signs and symptoms include nephrolithiasis (kidney stones), psychiatric disturbance, bony pain, and constipation. Treatment of hypercalcemia includes calcitonin, bisphosphonates, denosumab, furosemide, and corticosteroids.
• Renal failure: Multiple myeloma is associated with both acute renal failure and chronic renal failure. The mechanism of renal failure is usually due to abnormal deposition of immunoglobulin light chains in renal tubules, a process known as cast nephropathy. Signs and symptoms of renal failure include decreased urine output, volume overload, nausea, pruritic, metallic taste, and normocytic anemia due to erythropoietin deficiency.
• Neurologic complications: The effects of abnormal plasma cells on the nervous system can result in neurologic impairment. Multiple myeloma can cause neurologic complications via various mechanisms, including plasma cell infiltration of tissues of the central nervous system, plasma cell infiltration of tissues of the peripheral nerves (resulting in carpel tunnel syndrome), and osseous destruction in areas abutting nerve roots (resulting in radiculopathy), or osseous destruction in areas abutting the spinal cord (result in spinal cord compression).

Prognosis

The prognosis of multiple myeloma depends of a variety of factors. The most important factor that determines disease biology and prognosis is cytogenetics. Overall, prognosis is generally good with appropriate treatment. Without treatment, multiple myeloma will result in death with a median survival of 7 months. The 5-year overall survival rate of multiple myeloma is approximately 46%. However, the prognosis is far better in the current era since multiple new therapeutic interventions have been introduced.ublisher = | date = | accessdate = 17 February 2014 }}</ref>

• The table below lists common prognostic factors for multiple myeloma:

Prognostic Factor	Description
Stage	Advanced stages of multiple myeloma are associated with poor prognosis.
Kidney function	An elevated level of creatinine is associated with poor prognosis.
Labelling index	The labeling index indicates how fast the cancer cells are growing. A high plasma cell labeling index (PCLI) or proliferation (reproduction) rate is associated with poor prognosis.
Age	Older patients have worse prognosis than younger patients.
Chromosome changes	Cytogenetic analysis of multiple myeloma cells may be of prognostic value, with deletion of chromosome 13, non-hyperdiploidy and the balanced translocations t(4;14) and t(14;16) conferring a poorer prognosis. The 11q13 and 6p21 cytogenetic abnormalities are associated with a better prognosis.
Assocciated plasma cell disorder	The presence of plasma cell leukemia or soft tissue plasmacytoma is associated with a particularly poor prognosis among patients with multiple myeloma.
Performance status	Performance status is ranked on a 0–4 scale. The lower the number, the healthier and more active the person is, and the better the prognosis. Performance status is important in multiple myeloma because people who are healthier can withstand more intensive treatment.
Beta-2-microglobulin	A higher level of beta-2-microglobulin is associated with poor prognosis.
Albumin level	A lower albumin level is associated with poor prognosis.
Lactate dehydrogenase level	A higher level of lactate dehydrogenase (LDH) is associated with poor prognosis.
Response to treatment	People whose cancer responds to treatment and goes into complete remission have a better prognosis than people whose cancer does not respond to the initial treatment.

The prognosis for solitary plasmacytoma is generally very good. The median survival is 10 years. The 5-year survival rate is 72% and the 20-year survival rate is 37%.

References

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