Smoldering myeloma: a heterogeneous condition

Today I would like to summarise the salient point of a review article named “How I treat smouldering multiple myeloma (SMM)” published in 2014 and written by Irene Ghobrial and Ola Landgren. (1)  The main question we can see in this article is the following: Will the treatment of the precursor asymptomatic states of symptomatic myeloma, so the treatment of SMM, lead to the ultimate prevention of progression and cure in MM?
By way of a clinical case of a 42-year-old female patient, the authors start to describe the most important molecular and clinical points that characterise SMM, a precursor state of symptomatic multiple myeloma. 

Molecular mechanisms in SMM                                                                                                                             
Thanks to molecular techniques, such as the so-called Next-generation sequencing, it has been possible to see that in the bone marrow of patients with SMM there are many groups of tumor cells(subclones), that are heterogeneous. Furthermore, abnormalities in some chromosomes could appear in a progressive way by patients with SMM and influence its transformation into the dangerous symptomatic myeloma. 

How to diagnose patients with SMM                                                                                                                              
Although SMM is really heterogeneous, the International Myeloma Working Group established a consensus definition for the diagnosis of SMM in 2003. SMM was defined as either a concentration of M protein ≥3 g/dL in the blood or ≥10% monoclonal plasma cells in the bone marrow.

The role of imaging techniques                                                                                                                                     
To help the diagnosis and the periodic follow-up of patients with SMM, imaging techniques play an important role. For example, MRI is able to exclude the presence of lytic lesion, better than a traditional Rx skeletal survey.

How to estimate the risk of evolution by SMM patients                                                                                        
SMM heterogeneity is also notable in clinical manifestations of this condition. Indeed, you can have SMM very similar to the earlier precursor MGUS, which means a quiet condition.  On the other hand you could find more aggressive situations, that could require a stricter follow-up. Therefore, by a SMM it is really important to always estimate how high the risk to evolve into a symptomatic condition is. To do that, doctors normally use two useful score systems: the American system created by Mayo Clinic and the Spanish PETHEMA. 

Options of management in SMM: observation or early treatment?                                                                        
In 1990 the question “To treat or not to treat” early myeloma conditions, such as the state known as SMM at the present, appeared for the first time. The answer was negative first. (2)                                 
However, more efficient drugs are disposable nowadays, so that the treatment of SMM could be possible for types classified as “high risk” inside clinical trials. Obviously with interesting advantages. (3)

New sceneries in the near future                                                                                                                                       
It is very important to consider that SMM is a really heterogeneous condition and more studies are required before adopting new strategies in clinical practice. However, thanks to more and more accurate definitions of the risk of transformation into symptomatic myeloma and the knowledge of new drugs characteristics, it will be possible to reach other important goals by the prevention of symptomatic myeloma in the near future.


(1) How I treat smoldering multiple myeloma | Blood | American Society of Hematology (

(2) Hjorth M, Hellquist L, Holmberg E, Magnusson B, Rödjer S, Westin J; Myeloma Group of Western Sweden. Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I—a randomized study. Eur J Haematol. 1993; 50(2):95-102.

(3) Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013; 369(5):438-447.

About the author: Walter Bertolami

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