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]

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.

Table 5

Revised International Staging System for Myeloma

Stage	Frequency (% of patients)	5-year survival rate (%)
Stage 1 ISS Stage I (Serum albumin >3.5, Serum beta-2-microglobulin <3.5) and No high risk cytogenetics Normal LDH	28%	82
Stage II Neither Stage I or III	62%	62
Stage III ISS Stage III (Serum beta-2-microglobulin >5.5) and High risk cytogenetics [t(4;14), t(14;16), or del(17p)] or Elevated LDH	10%	40

From J Clin Oncol.^{37 PMID:26763514}

Risk Group	Percentage of newly diagnosed patients with the abnormality
Standard Risk	75%
Trisomies
t(11;14)
t(6;14)
Intermediate Risk	10%
t(4;14)
Gain(1q)
High Risk	15%
t(14:16)
t(14;20)
del(17p)

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.

Complications

Complications that can develop as a result of multiple myeloma are divided into:

• Local complications:

• Hematologic complications, results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal (hematopoiesis) by cytokines

• Normocytic normochromic anemia
• Bleeding disorders
• Pancytopenia due to bone marrow failure

• Skeletal complications

• Pathologic fractures
• Spinal cord compression present as back pain, numbness, dysthesias suggestive, loss of bowel or bladder control

• Systemic complications:

• Hypercalcemia
• Renal insufficiency, which may develop both acutely and chronically
• Neurologic complications

• Intracranial plasmacytoma
• Leptomeningeal involvement
• Retinopathy
• Radicular pain
• Carpal tunnel syndrome
• Paraplegia

• Infections

• Pneumonias
• Pyelonephritis
• Acute kidney injury

Prognosis

• The prognosis of multiple myeloma is good with treatment. Without treatment, multiple myeloma will result in death with a median survival of 7 months.
• Overall the 5-year survival rate of multiple myeloma is around 46.6%.
• Overall mortality rates peaked in the mid-1990s and have decreased in recent years with the development of new therapeutic interventions.
• The average survival of multiple myeloma patients is approximately 3 years and approximately 43.5% of patients survive after 5 years.

• 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.

References

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