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From Early Signs to Hematology Referrals

Optimizing Multiple Myeloma Diagnosis
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Understand Monoclonal Gammopathies
Identify the symptoms Early
Order recommended blood tests
Refer to hematology
Monitor MGUS patients
Populations at higher risk
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Suspecting and testing for complex conditions such as monoclonal gammopathies, including Multiple Myeloma can be challenging


Watch this short video for an overview of warning signs to diagnostic investigations, so you can help improve earlier diagnosis:

Understand monoclonal gammopathies

  • Monoclonal gammopathies, or plasma cell dyscrasias, are characterized by the overgrowth of a single plasma cell clone. These monoclonal plasma cells can secrete monoclonal proteins that are identified in blood samples.
  • Monoclonal gammopathies range from non-cancerous precursors like MGUS and Smoldering Multiple Myeloma to malignant forms like Multiple Myeloma, which can cause organ damage, severe symptoms, and be potentially fatal.
Figure adapted from Kumar1 Nat Rev Dis Primers 2017

Identify the symptoms early

  • Suspect Multiple Myeloma in patients presenting with back and bone pain, anemia, recurrent infections, general unwellness, fatigue, fractures, and renal impairment2.
  • Later presentation with advanced disease may be associated with end-organ damage. These are referred to as CRAB events: hypercalcemia, renal impairment, anemia, and bone lesions.

Order recommended blood tests

  • International3 and national4 guidelines recommend including serum free light chains (sFLC) testing alongside serum protein electrophoresis (SPE) and serum immunofixation (sIFE) when Multiple Myeloma is suspected to maximize the detection of monoclonal proteins.
  • The testing combination of serum free light chains (sFLC) and serum protein electrophoresis (SPE) has been shown to identify >99% of Multiple Myeloma patients5.

Dr Joseph Mikhael6, MD and Chief Medical Officer, International Myeloma Foundation recommended several blood tests to rule out Multiple Myeloma, in his recent publication . These include, but are not limited to:

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Complete blood count to check for anemia and raised Erythrocyte Sedimentation Rate (ESR)

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Chemistry to check for raised calcium, raised creatinine and low albumin

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Serum free light chain (sFLC) tests, serum protein electrophoresis (SPE) and immunofixation (sIFE) to check for a monoclonal protein

Figure adapted from Mikhael6 Am J Med 2023

Refer to hematology

  • Early referral and diagnosis of Multiple Myeloma are critical.
  • Delays can lead to severe comorbidities and reduced 5-year survival rates2, 7.
  • Timely intervention can markedly improve patient outcomes.
Diagram depicting why early referral and diagnosis of Multiple Myeloma are critical
Figure adapted from Rajkumar3 Lancet Oncol 2014 and NICE [NG35]4

Monitor MGUS patients

If an MGUS diagnosis is confirmed by hematologists, primary care providers may be asked to monitor these patients.

While MGUS is not a malignant condition, it has significant clinical implications. Patients with MGUS have an increased risk of progression to hematological malignancies8, such as Multiple Myeloma, as well as being more susceptible to infections9, renal impairment10, osteoporosis and fractures11, neurological disorders12 and thrombosis13.

Regular monitoring of these patients helps with early detection and treatment of more serious conditions that may develop.

Be aware of populations at higher risk of developing Multiple Myeloma

 

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Age14

Frequently diagnosed among those aged 65-74 years, although it can also occur in much younger individuals.
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Sex14

Slightly more common in men than women.
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Race6

African American patients have >2x the incidence rate compared to White patients, and tend to be diagnosed at a younger age relative to their White and Asian counterparts.
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Family History15

A family history of Multiple Myeloma or related plasma cell dyscrasia significantly increases the risk of developing Multiple Myeloma or MGUS. First-degree relatives of patients with Multiple Myeloma carry a 2 to 3 times higher risk of developing the disease.
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Precursor conditions16

Every patient with precursor conditions, such as MGUS or Smoldering Multiple Myeloma, carries a risk of progressing to Multiple Myeloma.


Download this reference tool to help improve earlier diagnosis

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References
  1. Kumar SK, et al. Multiple myeloma. Nat Rev Dis Primers 2017; 3:17046
  2. Hossain MI, et al. An in Depth Analysis of Factors Contributing to Diagnostic Delay in Myeloma: A Retrospective UK Study of Patients Journey from Primary Care to Specialist Secondary Care. Blood / Presented at ASH 2021; 138:3007a
  3. Rajkumar SV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15:e538-e548
  4. NICE. Myeloma: diagnosis and management [NG35]. NICE Guidelines 2016
  5. Katzmann JA, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem 2009; 55:1517-1522
  6. Mikhael J, Bhutani MCole CE. Multiple Myeloma for the Primary Care Provider: A Practical Review to Promote Earlier Diagnosis Among Diverse Populations. Am J Med 2023; 136:33-41
  7. Seesaghur A, et al. Clinical features and diagnosis of multiple myeloma: a population-based cohort study in primary care. BMJ Open 2021; 11:e052759
  8. Kyle RA, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 2010; 24:1121-1127
  9. Kristinsson SY, et al. Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study. Haematologica 2012; 97:854-858
  10. Leung N, et al. Monoclonal gammopathy of renal significance (MGRS): when MGUS is no longer undetermined or insignificant. Blood 2012; 120:4292-4295
  11. Kristinsson SY, et al. Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study. Blood 2010; 116:2651-2655
  12. Nobile-Orazio E. Neuropathy and monoclonal gammopathy. Vol. 115. 2013, Elsevier. p443-459
  13. Kristinsson SY, et al. Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood 2008; 112:3582-3586
  14. Ferlay J, et al. Global Cancer Observatory: Cancer Today (version 1.1). Lyon, France: International Agency for Research on Cancer. 2024 [Accessed on: 04/03/2024]; Available from: https://gco.iarc.who.int/today.
  15. Bhutani M, et al. Addressing the disparities: the approach to the African American patient with multiple myeloma. Blood Cancer Journal 2023; 13:189
  16. Kyle RA, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007; 356:2582-2590
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