At the 4th Annual International Myeloma Working Group Summit, which just wrapped up in Stockholm, important questions were again considered by over 70 IMWG myeloma researchers from 29 different countries. With a format structured to facilitate and encourage open discussion, the "hot topic" was clearly the diagnosis and management of high-risk smoldering or early active myeloma. 

In anticipation of the upcoming publication of the results of the University of Salamanca's  "High-Risk Smoldering Myeloma" trial, Dr. Maria-Victoria Mateos presented the results of the randomized trial showing survival benefit for high-risk smoldering myeloma patients receiving Lenalidomide-Dexamethasone therapy versus patients without therapy.

A concern voiced by many, including Maria-Victoria, is that although there is a survival advantage that is positive and encouraging this does not mean that this is a recommended approach. Quite the contrary, in fact! The focus of discussion was on how to identify patients who can be classified as having "early active myeloma," and select therapy appropriate for typical "symptomatic," so-called "CRAB positive" myeloma.  This would mean that lower-level smoldering patients would not be treated.

So two questions emerged: 1) How to define what is now being called "CRAB negative" myeloma--to be renamed henceforth as early active myeloma? and 2) Is normal myeloma therapy to be recommended for this new "CRAB negative" subgroup? This is when the discussion format--both in the open sessions and work groups--proved effective in soliciting the maximum input from the myeloma experts gathered at the IMWG Summit. Fortunately, there have been pertinent studies and publications to guide the way, especially from the Mayo Clinic and the University of Salamanca teams, as well as corroboration by teams from the U.S, NCI and the University of Athens.

A high risk of early active myeloma is, for example, linked to:

  • >60% plasma cells in the bone marrow, which carries a >90% risk of progression in 1 to 2 years
  • serum Freelite > 100 mg/dL FLC and FLC ratio > 100 (>80% chance of progression in 2 years)

There was also much discussion about whether additional criteria are necessary to accurately define early active myeloma. 

These are a couple of examples:

  • a PET/CT which shows active disease with evidence of bone destruction on CT (even if x-rays are negative) 
  • and/or  > a single focal "lesion" (or abnormality) on MRI imaging, this later being much less certain as a criterion.  

It was agreed that it is a priority to consider all these and additional parameters carefully as a basis to clearly define "early active myeloma" as soon as possible, using widely available testing procedures. There was also consensus among IMWG members that this subgroup is one of those most amenable to curative approaches to therapy, linking in directly with the IMF's Black Swan Research Initiative. 

Many more issues were raised and discussed. These will be the focus of future blog posts to give a full flavor of the diverse and important outcomes from this year's IMWG Summit. 

One simple and clear outcome is that everyone is already anticipating the IMWG Breakfast Meeting at the American Society of Hematology (ASH) annual meeting in New Orleans in December and ready to book their flights to Milan, Italy as soon as possible for the 2014 IMWG Summit!


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