The Latest Myeloma News from the American Society of Hematology Meeting

Andrew Schorr:

Dr. Lonial, here's a question we just got in from Jeanne from San Diego, and she says, 'Please define the term "high risk myeloma" that you may have used in this broadcast earlier.' What does "high risk myeloma" mean and maybe what does "smoldering" mean on the other side?

Dr. Lonial:

Yes, so let's start with smoldering first. Smoldering myeloma is by the new definitions is essentially what we call asymptomatic myeloma meaning that you have more than 10% plasma cells in the bone marrow, but you don't have any of the four cardinal symptoms that we use to distinguish symptomatic from asymptomatic myeloma. So, smoldering myeloma is in many ways a sort of pre-myeloma state where similar to the CLL that you were describing, we observe patients, and we don't treat them until they have true symptoms of active disease.

High-risk disease is really again it's a definition that nobody has clearly agreed upon, but if you look historically, patients with elevated beta-2 microglobulins, a marker that we use, patients with deletion of chromosome 13 by routine cytogenetics are considered high-risk disease, patients who have abnormalities of what's called the translocation between chromosomes 4 and 14 are considered high risk; patients who have what's called a removal of part of chromosome 17 are also considered potentially high-risk patients as well, and so there are a number of definitions. The group at Arkansas has identified a 17-gene signature from gene arrays that they use to identify a high-risk subset of patients. So, there are lots of differing opinions about what those definitions are, but I think what that tells us and what that tells me as a practitioner, is that all myelomas are not the same, and just as we've learned that about lymphomas and we've learned that about lung cancers and breast cancers that not all breast cancers are the same, it is probably the same for myeloma, and how many different subsets of myeloma there are probably depend in many ways on which categories you use to create those subdivisions, but I think one of the things that many of us think about at least is that we shouldn't be treating them all the same way.

We really should approach how we treat individual subsets in different ways, and the best example I can give you for that is patients with what's called hyperdiploid myeloma, good risk myeloma. Those patients actually have very good responses to melphalan-based therapy, and so those are patients who we wouldn't want to necessarily give up standard conventional chemotherapy even if you added new agents like bortezomib or lenalidomide to is, whereas other patients with very high-risk disease, abnormalities of their chromosomes, they don't have good responses at all to melphalan, and many could argue that they shouldn't even be considered for transplant independent of their age, and these are all risk stratification criteria that is an ongoing, moving process as we speak now, and in four or five years we'll probably be closer to saying you have type-A myeloma, you have type-B, you have type-C, and we know that patients with type-A get treated this way, and patients with type-B get treated a different way. Right now we just don't have that capability.

Andrew Schorr:

I will make one point though as a patient advocate, as you listen folks, though, you hear that these gentlemen who really focus almost totally, if not totally, on myeloma, they are slicing and dicing it in many different ways and trying to look for clues as to what to do for you, so if that is not the level of physician you have, somebody maybe more general, I would urge you to at least get a second opinion with a myeloma subspecialist in a time when so much is happening. It's really important, and it could make a critical difference for you and connect you with new regimens much sooner, and also I've always been told, I know my friends at MD Anderson like to say this and many of the major cancer centers, your first shot is your best shot. So, you really want to have a treatment plan for you that makes sense.

Here's a question, and I'll address this to Dr. Durie. This is from California, Tom from Murrieta, California. I'm not quite sure where that is. He says, 'What are the key factors to consider when deciding if and when it's time to go back on a treatment regimen after a treatment-free interval?' So, for instance, I know with Velcade you get to a certain level you can stop all treatment for a while. How do you know when you need to start again, Dr. Durie?

Dr. Durie:

This is obviously a key question for all patients with myeloma because the longer that you can safely stay off treatment, then you have a treatment-free interval, which obviously improves quality of life and you're ability to do the things that you need and want to do. On the other side of the coin, you don't want to delay treatment if you are really developing a medical problem, and so that is the key to the answer to this question. So, we now use not just the amount of the protein and the increase in the protein level, but what are called the "CRAB" criteria. These are the indicators that the myeloma is starting to impact your body. So, "C" is for calcium. Has the blood calcium gone up? "R" is for renal or kidney function. Has the serum creatinine, kidney function test, gone up? "A" is for anemia, and "B" is for bone disease. So, as the disease is being tracked, it's really crucial to see what is the impact on these parameters, and although in these trials that we've been talking about, these large trials and some smaller trials, relapse is defined as just the increase in the protein level, but actually need for therapy is a little bit different even though the protein level may be creeping up, if one of those other CRAB features has not emerged, it may be possible to monitor closely and delay the time that new treatment needs to be considered.

Obviously, when the protein level is going up, testing needs to be done to make sure that one of these things I mentioned is not happening.

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Page last updated on November 22, 2013