When patients test as having borderline high-risk smoldering myeloma, should they receive treatment?

Should borderline high-risk smoldering myeloma patients receive treatment? 

Dr. Brian G.M. Durie discusses if patients with borderline high-risk smoldering myeloma should start treatment early.


Monitor your myeloma-levels closely. Discuss your options carefully with your doctor and decide if treatment is necessary.

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This week's "Ask Dr. Durie" comes from a patient worried about the possible diagnosis of high-risk smoldering myeloma, what we call HRSMM. And so, this is an increasingly common question for patients who maybe have borderline evidence of myeloma based on the percentage of plasma cells in the bone marrow or the level of the myeloma protein in the blood. And so, the question is: How do you move forward with this information?

And so, this patient is aware that we do have information that some treatments can be helpful for patients with high-risk smoldering myeloma. 

There was a randomized trial in Spain, where patients received Revlimid® versus nothing, and giving the Revlimid early to patients with high-risk smoldering myeloma resulted in longer remissions in improved some survival. And there has been a similar study conducted by the Eastern Oncology Cooperative Group here in the U.S., also looking at the benefit of Revlimid. And so, we do evidence of benefit for early therapy.

But two very, very, important questions remain. The first question is: How do we determine that a patient has high-risk smoldering myeloma? And that is the question this patient is asking. Because right now we’re using these criteria called the 2/20/20 criteria, based upon the level of myeloma protein in the blood, two grams per deciliter or not, the percentage of plasma cells in the bone marrow, twenty percent or not, or the Freelite ratio, involved over uninvolved twenty or not, or higher for these different numbers. 

And so, you can see right away problems that emerge. Sometimes a patient's numbers can be borderline. So, what do you do if your plasma cell percentage is nineteen percent? That doesn’t meet the criteria. What about if your spike is one point eight? It’s not two. So, you can see that there are some really difficult, borderline decisions. And so, for sure, we do not want to give treatment where there is a borderline possibility that maybe the smoldering myeloma is going to continue to smolder without treatment.

And so, initial monitoring is always recommended. Double-check those labs, repeat the blood levels, for example. We don’t want to rush to be constantly repeating the bone marrow. But, if there is doubt, it’s always much safer to monitor closely than intervene without clear knowledge. 

And so, the second major issue is if you are going to treat. If you’ve decided, oh my gosh, the number is increasing and they are way beyond twenty, twenty, and two, which treatment should you use? And so, here, trials are going on to see if you could take VRd versus Rd, basically a myeloma treatment. And there are these ongoing cure trials, where, in Spain, KRd plus transplant was given with excellent results. And in the U.S., we have the ASCENT trial in which excellent results are being achieved with daratumumab, KRd, and it will be plus or minus transplant. 

And so, these are things which you can see immediately require, as a BOTTOM LINE here, careful discussion with your doctor. And with caution about jumping in too soon would be my number one recommendation. Talk to your doctor, monitor your numbers. Try to have some sense that if you are going to treat, that the disease is truly showing indications of change. And then, select the treatment based upon discussions with your doctor. You might want to use a gentler approach, like just lenalidomide, or even VRd, versus a more aggressive approach, where there is an intent to achieve an MRD-negative status or to push to achieve cure. This is a special approach and a special situation that needs careful discussion. So, please discuss these two major points: Do you have high-risk smoldering? And what would be a treatment option if there is an idea to move forward? And, really have a joint and careful plan with your doctor. 



Image of Dr. Brian G.M. DurieDr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.


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