Smoldering Myeloma and MGUS: Why Watch and Wait?

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Topics include: Treatments

Watch and wait can be a daunting time. What does it mean? What are you waiting for? Dr. Robert Orlowski from MD Anderson Cancer Center and Dr. Paul Richardson from Dana-Farber Cancer Institute, define the terms MGUS and smoldering myeloma. The experts share the reasoning behind the watch and wait period, how patients should be monitored, and address concerns in both high-risk and asymptomatic myeloma.  The experts also discuss clinical trials that are being conducted to answer the questions of who to treat and when to treat. 

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Jack Aiello:

Dr. Orlowski, some of us are diagnosed with what might be a precursor to myeloma.  Some will hear a term called MGUS.  Some might hear smoldering, and their doctor will say, “Well, we should just watch and wait.” And we patients kind of look at it and say, “What do you mean watch and wait? Why don’t we fix it early?”  Can you talk a little bit more about terms like smoldering, and should we be watching and waiting?

Dr. Orlowski:     

Yeah. Great question. You mentioned MGUS, which is monoclonal gammopathy of undetermined significance, which is a fancy way to say that there’s a usually low level of an abnormal protein in the blood, but it probably doesn’t mean anything. And actually, if we do that protein electrophoresis and immunofixation on people who are of the level of maturity of all of us in this room, probably about 3 or 4 percent would have an abnormal protein of this type.

But the vast majority of them would never progress to multiple myeloma. And right now, for MGUS, the standard is still to do a watch and wait because, again, the risk of progression is only about 1 percent per year.  Smoldering myeloma is a little bit different, because these are people that have higher levels of, for example, bone marrow involvement and, usually, a higher level of the protein that we’re looking for in the blood. 

First of all, one thing to remember is that the category of smoldering has recently been redefined so that some of what previously used to be high-risk smoldering patients have now been classified as having active myeloma and should probably, therefore, now be treated. So if you were diagnosed let’s say more than six months or a year ago, you should make sure to talk to your doctor about whether if you were previously diagnosed as smoldering, if you’re still in that category.

If you were diagnosed more recently, and you do have the smoldering, and some of us prefer to use the term asymptomatic, the smoldering sort of sounds like a brush fire ready to erupt, which none of us really like to do? But if you have asymptomatic myeloma, there are some people who are in that category who are still at high risk of progression. And there are a number of studies and treatment approaches that are being looked at to see if perhaps treating those people early could delay the time until they progress. And maybe even those would be people whose treatment could result in a cure, although I don’t think we’re quite that far yet.  

Jack Aiello:         

So for the ultra high-risk asymptomatic, they now might be myeloma patients.

So you can be a myeloma patient without having symptoms. And for the high-risk smoldering, asymptomatic patients, there are trials to try to answer the question of should you treat now or later.

Dr. Richardson:

That’s correct, Jack. And I think the important point here to echo Bob’s point earlier about this asymptomatic disease is there are a couple of ways of thinking of this.  There’s a lovely old term that a stitch in time saves nine. And the issue is that is there a group of patients in whom some form of early intervention will help them in terms of long-term outcome? And in the field right now, it’s an area of very active research. Who benefits from what when? And the question is, in high-risk asymptomatic myeloma that’s very likely to progress to active disease, are there treatment strategies that can help people?

And we’ve got some very provocative information from colleagues in Europe, specifically from the Spanish group, suggesting that some of our newer treatments earlier that are relatively non-toxic and well tolerated can, in fact, result in survival benefits, specifically, the use of lenalidomide (Revlimid) with dexamethasone (Decadron) was compared to observation.

And in that particular trial, benefit was seen to the treatment arm that was substantial, actually, and resulted in survival differences in favor of the pills.  Now, the interesting question there though was how was the control arm treated? And they were simply observed. And the way the trial was written was that, actually, the observation arm was quite strict.  They could just be observed. And I think when we look at that trial in its totality, you realize that the control group and the treatment group both shared features that were very concerning for what we would now consider active myeloma.

And so this is a critical point. Who do we treat when with what and how early?  So we’re trying to redefine this area so that we’re better at picking out who is it who will potentially run into trouble versus those who might not.

And the exciting news for patients, I think, is that we have treatment options, Jack, that are really well tolerated in this setting. We’ve been doing some work, and I know Bob’s team [has] been doing this as well, using immunotherapeutic strategies early.  For example, monoclonal antibodies early, immunomodulators like lenalidomide early.  And even the idea of also using anti-tumor vaccines.  So these are relatively non-toxic approaches that can harness or unleash the immune system early in this disease process. So there’s a lot of excitement in this area, and I think it’s very promising for the future.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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Page last updated on August 27, 2015