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MGUS (Monoclonal gammopathy of undetermined significance) - > Smoldering Myeloma -> Multiple Myeloma

Updated: Mar 8

MGUS (Monoclonal gammopathy of undetermined significance) - > Smoldering Myeloma -> Multiple Myeloma

MGUS MULTIPLE MYELOMA

 

MGUS Diagnosis:


Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic premalignant clonal plasma cells disorder. MGUS evolves into active Multiple Myeloma based on the Risk factors, in some individuals.


MGUS is defined by the presence of:

  • a serum monoclonal protein (M protein) at a concentration <3 g/dL

  • a bone marrow with <10 percent monoclonal plasma cells and

  • absence of myeloma defining events

Read more:

What are myeloma defining events? The SLiM-CRAB Criteria


Monoclonal gammopathy of undetermined significance (MGUS) is present in over 3% of the population above the age of 50 and the prevalence is approximately 2-fold higher in blacks compared with whites.


MGUS progresses to multiple myeloma at a rate of 1% per year. MGUS is asymptomatic, and is sometimes incidentally diagnosed on routine lab tests ordered by physicians for some other reasons.


The rate of progression is influenced by the underlying cytogenetic type of disease; patients with t(4;14) translocation, del(17p), and gain(1q) are at a higher risk of progression from MGUS or SMM to multiple myeloma.


 

SMM Diagnosis:


In some patients, an intermediate asymptomatic, but more advanced pre-malignant stage is referred to as smoldering multiple myeloma, (SMM), This can be recognized clinically.


SMM is defined by the presence of:


  • a serum monoclonal protein (M protein) at a concentration >3 g/dL and / or

  • bone marrow with 10 - 60 % monoclonal plasma cells and

  • absence of myeloma defining events

Read more:

What are myeloma defining events? The SLiM-CRAB Criteria


Smoldering multiple myeloma progresses to multiple myeloma at a rate of approximately 10% per year over the first 5 years following diagnosis, 3% per year over the next 5 years, and 1.5% per year thereafter.


The rate of progression is influenced by the underlying cytogenetic type of disease; patients with t(4;14) translocation, del(17p), and gain(1q) are at a higher risk of progression from MGUS or SMM to multiple myeloma.


What is High Risk Smoldering Myeloma?


  • a serum monoclonal protein (M protein) at a concentration >3 g/dL and / or

  • bone marrow with greater than 10 % monoclonal plasma cells


and presence of any two or more of the following: (20 /2/20 risk Stratification)

  • Bone marrow plasma cells > 20%

  • M Protein >2 g/dl

  • Involved/Uninvolved Free Light Chain Ratio > 20

 

MM Diagnosis:


  • ≥10% bone marrow plasma cells or

  • a biopsy proven plasmacytoma

Plus

  • evidence of one or more myeloma defining events

  • a serum monoclonal protein (M protein) at any concentration


Read more:

What are myeloma defining events? The SLiM-CRAB Criteria


The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma.

 

Multiple myeloma: 2020 update on diagnosis, risk-stratification and management

Am J Hematol, 2020 May

https://pubmed.ncbi.nlm.nih.gov/32212178/

https://onlinelibrary.wiley.com/doi/10.1002/ajh.25791



Multiple myeloma current treatment algorithms

Blood Cancer Journal 2020 Sep

https://www.nature.com/articles/s41408-020-00359-2






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