Evaluating Risk and Progression in High-Risk Smoldering Myeloma 

This week's "Ask Dr. Durie" comes from a patient who is very interested in high-risk smoldering multiple myeloma, and specifically about how secure is the doctor when they say that a patient has high-risk smoldering multiple myeloma? And this is important because these days there are a number of protocols to recommend treatment options for patients with high-risk smoldering multiple myeloma. 

And one needs to be secure that there is a need for this kind of therapy. And so, high-risk smoldering is a situation where there is evidence of some aspects of myeloma, but no CRAB criteria, no indications of activity destroying bones, causing anemia or the like. The criteria that we use to say that someone has high-risk smoldering are indicators that would suggest that myeloma will emerge within 12-to-18 months. 

The criteria that we currently use are the 20/2/20 criteria. The two is the level of the "m" component, the myeloma protein in the blood. The 20 is the percentage of plasma cells in the bone marrow, and the other 20 is the free light ratio. The abnormal over the normal. And using these indicators, patients with these numbers or higher fall into the category of being likely to develop active myeloma within 12-to-18 months. 

And this is the kind of patients where discussions are frequently held to see whether early active treatment could be helpful in achieving a really excellent result, even in an effort to try to cure such a patient. Questions have been raised as to whether or not this 20/2/20 system is reliable enough. And there are other systems that doctors can use. 

And so, I think it is a very reasonable question for this patient. What I can tell you is that using the to 20/2/20 system, having a risk score of at least 12 is really quite secure. Such patients, 70-to-80% of these patients will in fact develop active myeloma within a year. And so, patients in this group can be quite secure that the risk is indeed true and important in terms of decision making. 

 For other categories, there is a need to try to improve to be a little bit more secure beyond the 50/50 risk level. And so, the IMWG members and the subcommittee are actively looking at new methods. One of the methods is to follow patients for six months to one year to be sure that perhaps there is evidence of early progression. And another new idea, which I think will turn out to be perhaps the most important, is to see if there are myeloma cells in the blood and how many myeloma cells there are in the blood. 

We have indications from studies by several experts now which indicate that if there are myeloma cells in the blood, this does reliably indicate a trend towards active myeloma. And so, these kinds of testing are now being evaluated and will likely be implemented soon. 

And so, the BOTTOM LINE for this patient today is that this is a very important question. 

We are looking at the reliability of the 20/2/20 system, which is reliable, particularly for the higher risk groups such as 12 risk score or better. But we are looking for improvements. And if there is any doubt for sure there should be a decision to watch and wait and make sure what is the status of the patient. The main thing is to be sure that no CRAB criteria are emerging. 

We do not want patients to evolve such that they might develop bone lesions or kidney problems or some other indications of active myeloma. So it is a fine line and we will be very keen to see our new studies and to see if we can do as good a job as possible to accurately predict patients who do indeed have high-risk smoldering myeloma.