Multiple myeloma overview

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Epidemiology and Demographics

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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

Multiple myeloma is a type of cancer of plasma cells which are immune system cells in the bone marrow that produce antibodies. Multiple myeloma is part of the broad group of diseases called hematological malignancies. There are no established causes for multiple myeloma. Multiple myeloma must be differentiated from monoclonal gammopathy of undetermined significance(MGUS), isolated plasmacytoma of the bone, and extramedullary plasmacytoma.[1] The most potent risk factor in the development of multiple myeloma is old age.[2][3][4] 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.[5][6] Multiple myeloma is the second most common blood cancer after non-Hodgkin's lymphoma & 14th most common cancer overall in United States.[7][8][9] There is insufficient evidence to recommend routine screening for multiple myeloma.[10][11] If left untreated, most of patients with multiple myeloma may progress to develop fatigue, bone pain, and pallor.[9] Multiple myeloma may be divided into three stages based on either the International Staging System or Durie-Salmon Staging System.[12] The most common symptoms of multiple myeloma include bone pain, pallor, and fatigue.[9][13][14] Patients with multiple usually appear fatigued and lethargic.[9][13] Laboratory findings consistent with the diagnosis of multiple myeloma include abnormal complete blood count, erythrocyte sedimentation rate (ESR), basic metabolic panel, electrophoresis and immunohistochemistry.[13][9] Pharmacological regimes for patients with active (symptomatic) multiple myeloma include steroid therapy, immune modulator therapy, and chemotherapy.[15][16] Whereas patients with smoldering (asymptomatic) multiple myeloma are managed by observation and undergoing follow up tests every 3 to 6 months.[15][16]

Pathophysiology

Multiple myeloma arises from post-germinal center B lymphocytes, that are normally involved in production of human immunoglobulins.[3][9][17][18]Development of multiple myeloma is the result of multiple genetic translocation between the immunoglobulin heavy chain gene and oncogenes which leads to dysregulated multiplication of plasma cells.[9][17] On microscopic histopathological analysis, abundant eosinophilic cytoplasm, eccentrically placed nucleus, and russell bodies bodies are characteristic findings of multiple myeloma.[19]

Causes

There are no established causes for multiple myeloma.

Differentiating Multiple Myeloma from other Diseases

Multiple myeloma must be differentiated from monoclonal gammopathy of undetermined significance(MGUS), isolated plasmacytoma of the bone, and extramedullary plasmacytoma.[20]

Epidemiology and Demographics

In 2012, the incidence of multiple myeloma was approximately 6.3 per 100,000 cases with a mortality rate of 3.3 per 100,000 cases in the United States.[21] The prevalence of multiple myeloma was estimated to be 89,658 cases in 2012 in the United States.[22][9] Multiple myeloma is the second most common blood cancer after non-Hodgkin's lymphoma & 14th most common cancer overall in United States.[7][23][9] Male are more commonly affected with multiple myeloma than female. The male to female ratio is approximately 1.54 to 1.[9][3] Multiple myeloma usually affects individuals of the African American and Native Pacific Islanders race. Asian individuals are less likely to develop multiple myeloma.[9] The incidence of multiple myeloma increases with age; the median age at diagnosis is between 65 to 70 years years.[9]

Risk Factors

The most potent risk factor in the development of multiple myeloma is old age. Other risk factors include positive family history, positive history of monoclonal gammopathy of undetermined significance (MGUS), and occupational exposure to radiation and toxic chemicals.[9][3][24]

Screening

There is insufficient evidence to recommend routine screening for multiple myeloma.[25][26]

Natural History, Complications and Prognosis

If left untreated, most of patients with multiple myeloma may progress to develop fatigue, bone pain, and pallor.[9] Complications that can develop as a result of multiple myeloma are anemia, renal failure, skeletal complications, and neurological complications.[27] 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.[28][29] Multiple myeloma is associated with a 10 year survival of 3%. The presence of plasma cell leukemia or soft tissue plasmacytomas is associated with a particularly poor prognosis among patients with multiple myeloma.[30] According to a report published by National Cancer Institute there is a 43.25% chance of 5 year survival.[31]

Diagnosis

Diagnostic Criteria

The International Myeloma Working Group (IMWG) proposed updated criteria for the diagnosis of multiple myeloma in November 2014. The diagnosis requires >10% clonal plasma cell proliferation in the bone marrow, or biopsy-proven plasmacytosis at an extramedullary site plus one of more of the multiple myeloma-defining CRAB features (hypercalcemia, renal failure, anaemia, and bone lesions) or one or more of the newly added biomarkers of malignancy (clonal bone marrow plasma cell percentage ≥60%, involved:uninvolved serum free light chain ratio ≥100, and >1 focal lesions on MRI studies).[32]

Staging

Multiple myeloma may be divided into three stages based on either the International Staging System or Durie-Salmon Staging System.[33] The International Staging System for multiple myeloma was published by International Myeloma Working Group in 2003 and is the most widely used staging system.[34][35] It is used for both guiding treatment as well as predicting prognosis. The Durie-Salmon staging system, first published in 1975, is a clinical staging system for multiple myeloma that correlates measured myeloma cell mass to the presenting clinical features, response to treatment, and survival.[36] Durie-Salmon Staging System is still in use, but has been largely superseded by the more practical ISS.[37]

History and Symptoms

The most common symptoms of multiple myeloma include bone pain, pallor, and fatigue.[9][13][38] However, the presenting symptoms of multiple myeloma may vary greatly due to involvement of many organ systems. The common symptoms of multiple myeloma can be remembered by the mnemonic CRAB - C = Calcium (elevated), R =Renal failure, A = Anemia, B = Bone lesions.[39][13][40]

Physical Examination

Patients with multiple usually appear fatigued and lethargic.[9][13] Physical examination of patients with multiple myeloma is usually remarkable for pallor, purpura, hepatosplenomegaly, carpal tunnel syndrome, and signs of cord compression.[9][13] Any of these physical findings may warrant further evaluation, and thus leads to an incidental diagnosis of multiple myeloma.

Laboratory Findings

Laboratory findings consistent with the diagnosis of multiple myeloma include abnormal complete blood count, erythrocyte sedimentation rate (ESR), basic metabolic panel, electrophoresis and immunohistochemistry. An elevated concentration of serum protein level without concomitant elevation of serum albumin level is very suggestive of multiple myeloma.[13][9]

X Ray

X-ray may be helpful in the diagnosis of multiple myeloma. Findings on X-ray suggestive of multiple myeloma include punched out bony lesions, generalized osteopenia, and hair on end appearance.[3]

CT

CT scan does not have a great role in the diagnosis of disseminated multiple myeloma.[3]

MRI

MRI may be diagnostic of multiple myeloma. Findings on MRI suggestive of multiple myeloma include infiltration and replacement of the bone marrow.[3]

Other Imaging Findings

Positron Emission Tomography (PET) scan may be diagnostic of multiple myeloma.[13][3][41][42] Findings on PET scan suggestive of multiple myeloma include uptake of the F18-FDG molecule by lesions of bone lysis seen on PET-CT scan.[3]

Other Diagnostic Studies

Biopsy and genetic testing may be helpful in the diagnosis of multiple myeloma.[13] On bone marrow biopsy, multiple myeloma is characterized by an increase in percentage of abnormal plasma cells.[13] On genetic testing, multiple myeloma is characterized by chromosome 13 deletion and chromosome 14 translocation.[13][9]

Treatment

Medical Therapy

Pharmacological regimes for patients with active (symptomatic) multiple myeloma include steroid therapy, immune modulator therapy, and chemotherapy.[15][16] Whereas patients with smoldering (asymptomatic) multiple myeloma are managed by observation and undergoing follow up tests every 3 to 6 months.[15][16] The optimal therapy for active multiple myeloma depends on whether or not a patient is eligible for bone marrow transplantation.[15][16] Pharmacologic medical therapy for active multiple myeloma patients who are eligible for a bone marrow transplant include either dexamethasone, lenalidomide, bortezomib, thalidomide, carfilzomib, cyclophosphamide, vincristine, or doxorubicin.[15][16] In addition to the aforementioned agents, pharmacological regimes used for treatment of active multiple myeloma patients who are not eligible for a bone marrow transplant include either melphalan or prednisone.[15][16] Alkylating agents are not recommended among transplant eligible patients, as the toxicity of such agents makes the harvest process of bone marrow stem cell difficult later in the course of the disease.[15][16]

Surgery

Surgery is not a main treatment for multiple myeloma. Emergency surgery may be needed to help support weight-bearing bones in the spine or legs to prevent bones from breaking.

References

  1. ↑ "Myeloma - SEER Stat Fact Sheets". Retrieved 17 February 2014.
  2. ↑ Press Releases. Compugen (2015)http://www.cgen.com/media-center/press-releases/-314 Accessed on September, 20th 2015
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015
  4. ↑ Multiple myeloma. The American Cancer Society (2015) http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-risk-factors Accessed on September, 20 2015
  5. ↑ Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015
  6. ↑ Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit&section Accessed on September, 20th 2015=1
  7. ↑ 7.0 7.1 Collins, CD. (2005). "Problems monitoring response in multiple myeloma". Cancer Imaging. 5 Spec No A: S119–26. doi:10.1102/1470-7330.2005.0033. PMID 16361127.
  8. ↑ Seer stat fact sheet. National cancer institute (2015)http://seer.cancer.gov/statfacts/html/mulmy.html Accessed on September, 20th 2015
  9. ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.17 9.18 Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015
  10. ↑ Multiple Myeloma Prevention and Screening.(2015)http://www.mdanderson.org/patient-and-cancer-information/cancer-information/cancer-types/multiple-myeloma/prevention/index.html
  11. ↑ Can multiple myeloma be prevented?(2015)http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-prevention
  12. ↑ About multiple myeloma. University of California San Francisco (2015)http://cancer.ucsf.edu/research/multiple-myeloma/ Accessed on September, 18 2015
  13. ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 13.11 Multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/signs-and-symptoms/?region=mb Accessed on September 20th 2015
  14. ↑ Multiple myeloma. Cancer. gov(2015) http://www.cancer.gov/types/myeloma Accessed on September, 20th 2015
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 15.6 15.7 Treatment guide active multiple myeloma. National comprehensive cancer network(2015) http://www.nccn.org/patients/guidelines/myeloma/#44/z Accessed on September, 20th 2015
  16. ↑ 16.0 16.1 16.2 16.3 16.4 16.5 16.6 16.7 Treatment guide smoldering multiple myeloma. National comprehensive cancer network(2015) http://www.nccn.org/patients/guidelines/myeloma/#44/z Accessed on September, 20th 2015
  17. ↑ 17.0 17.1 Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html Accessed on September, 20th 2015
  18. ↑ Multiple myeloma. National cancer institute (2015) Accessed on September, 20th 2015
  19. ↑ Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit&section=1
  20. ↑ "Myeloma - SEER Stat Fact Sheets". Retrieved 17 February 2014.
  21. ↑ Plasma cell neoplasm.National cancer institute (2015)http://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#cit/section_1.1
  22. ↑ Seer stat fact sheet. National cancer institute (2015)http://seer.cancer.gov/statfacts/html/mulmy.html Accessed on September, 20th 2015
  23. ↑ Seer stat fact sheet. National cancer institute (2015)http://seer.cancer.gov/statfacts/html/mulmy.html Accessed on September, 20th 2015
  24. ↑ Multiple myeloma. The American Cancer Society (2015) http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-risk-factors Accessed on September, 20 2015
  25. ↑ Multiple Myeloma Prevention and Screening.(2015)http://www.mdanderson.org/patient-and-cancer-information/cancer-information/cancer-types/multiple-myeloma/prevention/index.html
  26. ↑ Can multiple myeloma be prevented?(2015)http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-prevention
  27. ↑ Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015
  28. ↑ Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015
  29. ↑ Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit&section Accessed on September, 20th 2015=1
  30. ↑ Plasma cell neoplasm. Cancer.gov (2015)http://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015
  31. ↑ Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015
  32. ↑ Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548
  33. ↑ About multiple myeloma. University of California San Francisco (2015)http://cancer.ucsf.edu/research/multiple-myeloma/ Accessed on September, 18 2015
  34. ↑ Greipp PR, San Miguel J, Fonseca R, Avet-Loiseau H, Jacobson JL, Rasmussen E, Crowley J, Durie BMG. Development of an international prognostic index (IPI) for myeloma: report of the international myeloma working group. Hematology Journal 2003;4:S42. NLM ID 100965523.
  35. ↑ About multiple myeloma. University of California San Francisco (2015)http://cancer.ucsf.edu/research/multiple-myeloma/ Accessed on September, 18 2015
  36. ↑ Durie BG, Salmon SE (1975). "A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival". Cancer. 36 (3): 842–54. PMID 1182674.
  37. ↑ About multiple myeloma. University of California San Francisco (2015)http://cancer.ucsf.edu/research/multiple-myeloma/ Accessed on September, 18 2015
  38. ↑ Multiple myeloma. Cancer. gov(2015) http://www.cancer.gov/types/myeloma Accessed on September, 20th 2015
  39. ↑ International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749-57. PMID 12780789.
  40. ↑ Multiple myeloma. Cancer. gov(2015) http://www.cancer.gov/types/myeloma Accessed on September, 20th 2015
  41. ↑ Shortt CP, Gleeson TG, Breen KA, McHugh J, O'Connell MJ, O'Gorman PJ; et al. (2009). "Whole-Body MRI versus PET in assessment of multiple myeloma disease activity". AJR Am J Roentgenol. 192 (4): 980–6. doi:10.2214/AJR.08.1633. PMID 19304704.
  42. ↑ Agarwal A, Chirindel A, Shah BA, Subramaniam RM (2013). "Evolving role of FDG PET/CT in multiple myeloma imaging and management". AJR Am J Roentgenol. 200 (4): 884–90. doi:10.2214/AJR.12.9653. PMID 23521465.


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