Understanding Multiple Myeloma


Symptoms, manifestations and complications

Statistics

Worldwide yearly incidences of Multiple Myeloma

 

160 K
cases
2 %
all cancer diagnoses
3 rd
most common haematological malignancy¹
6 th
decade of life, equals median age of detection

What is it

Multiple Myeloma (MM) is a malignant cancer of plasma cells, the cells responsible for antibody production

When there is an expansion of a plasma cell clone in the bone marrow, monoclonal proteins can be produced at high levels. These monoclonal proteins, also referred to as M-proteins or paraproteins, can be intact immunoglobulins or free light chains.

Multiple Myeloma can affect several bony areas of the body, such as the spine, skull, pelvis, and ribs.a The symptoms of MM are caused by both the growth of the tumour itself (and its effects on the bone structure and the bone marrow microenvironment), and the effect of the monoclonal proteins on other organs.b It can lead to bone fractures, kidney damage, anemia and impaired immune function.c

Symptoms and clinical impact of Multiple Myeloma

Can be difficult to diagnose because the symptoms are non-specific and often associated with the effects of ageing

Early referrals to hematologists and cancer care have the potential to improve the overall survival and quality of life for patients, but this requires early recognition of the symptoms and confirmation of the Multiple Myeloma diagnosis.

Most of the symptoms and complications of MM are caused by either the effect of the tumor on the surrounding bone and the bone marrow microenvironment or by the effect of monoclonal proteins on other organs. The most common symptom of MM is pain in bones (usually hips, spine, ribs, and skull).

Changes to the bone marrow microenvironment also affect the production of blood cells, causing anaemia and reduced immune system function with increased infections. Myeloma cells can also heavily damage bone structure, leading to hypercalcemia and an increased risk of fractures.

The monoclonal proteins produced can damage organs, most commonly the kidney. This is why many myeloma patients suffer from renal impairment, including damage so severe it requires dialysis2.

A variety of tests – including a bone marrow biopsy, and blood and skeletal analyses – will confirm if any CRAB symptoms are present

Clinical manifestations

CRAB Symptoms

Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder is part of the diagnostic criteria for multiple myeloma. A mnemonic for remembering this group of symptoms is CRAB.

HyperCalcemia

Elevated calcium in the blood

Renal insufficiency

Improper kidney function

Anemia

Red blood cell deficiency

Bone lesions

Abnormal tissue mass within a bone2

SLiM Criteria

Historically, myeloma patients had poor physical condition when they were diagnosed due to the presence of this end organ damage. In order to enable treatment before end organ damage occurred, biomarkers were identified to indicate patients who were at high risk of developing end organ damage within a short time. These biomarkers of malignancy are referred to as the SLiM criteria.3

Sixty

Patient has ≥60% clonal bone marrow plasma cells in bone marrow biopsy samples

Light chain

Involved/uninvolved serum free Light chain ratio ≥ 100, provided the involved FLC ≥ 100 mg/L

MRI

patient has >1 bone lesion by MRI3

Together, the CRAB and SLiM criteria are referred to as myeloma defining events (MDE). In order to be diagnosed with Multiple Myeloma, a patient must have ≥10% clonal bone marrow plasma cells (or a biopsy-proven bony or extramedullary plasmacytoma) and at least one MDE.

Complications

Complications of Multiple Myeloma 

  • Frequent infections (immune suppression)
  • Bone problems
  • Reduced kidney function (cast nephropathy)
  • Heart failure/Cardiac damage due to AL Amyloidosisd (AL amyloidosis is another monoclonal gammopathy, which can co-occur with MM
  •  Low red blood cell count (anemia)1

Multiple Myeloma and Monoclonal Gammopathies

Challenges with traditional monitoring
What is the best test combination to rule out Multiple Myeloma?
Why is Multiple Myeloma so difficult to diagnose?

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3rd Party Websites
a. https://www.cancerresearchuk.org/health-professional/cancer-statistics/incidence/common-cancers-compared#heading-Zero
b. https://www.nhs.uk/conditions/multiple-myeloma/
c. https://themmrf.org/multiple-myeloma/
d. https://www.amyloidosis.org.uk/about-amyloidosis/al-amyloidosis/symptoms-and-signs-of-al-amyloidosis/
References
1. Bird SA & Boyd K. Multiple myeloma: an overview of management. Palliat Care Soc Pract 2019; 13:1178224219868235
2. Kariyawasan CC, et al. Multiple myeloma: causes and consequences of delay in diagnosis. QJM 2007; 100:635-640
3. Rajkumar SV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15:e538-e548