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New Thinking on Asymptomatic Myeloma

Panelists:Keith Stewart, MD, CHB, Mayo Clinic;William I. Bensinger, MD, Swedish Cancer Institute;Rafael Fonseca, MD, Mayo Clinic;C. Ola Landgren, MD, PhD, Memorial Sloan Kettering Cancer Center;Jatin P. Shah, MD, MD Anderson Cancer Center
Published: Monday, Jun 27, 2016


Transcript:

Keith Stewart, MD, CHB:
Hello, and thank you for joining us today for this OncLive Peer Exchange Panel Discussion on the topic of multiple myeloma. These are exciting times in the field of multiple myeloma research, with several new agents approved by the FDA in 2015. However, along with this unprecedented progress comes increased complexity in terms of choosing the best course of therapy for an individual patient. In this OncLive Peer Exchange, I am joined by a panel of experts in the field of myeloma. Today, we will discuss how the changes in NCCN guidelines and the introduction of new data from the ASCO 2016 meeting will affect routine clinical practice.

My name is Dr. Keith Stewart, and I’m the Vasek and Anna Maria Polak Professor of Cancer Research at the Mayo Clinic. Participating today on our distinguished panel is Dr. William Bensinger, chief of the myeloma program at the Swedish Cancer Institute in Seattle, Washington; Dr. Rafael Fonseca, a Getz Family Professor of Cancer and the chair of the Department of Medicine at the Mayo Clinic in Arizona; Dr. Ola Landgren, professor of medicine and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center in New York; and, of course, Dr. Jatin Shah, associate professor of medicine at the MD Anderson Cancer Center in Houston, Texas. Thank you for joining us, and let’s get started.

I wanted to start perhaps by talking about some changes in how we think about who actually has myeloma in the first place that may or may not require therapy. Dr. Landgren, I’m looking at you because you’ve been quite active in this field. Can you explain to the audience what’s changed recently and who we think actually has myeloma that needs therapy?

C. Ola Landgren, MD, PhD: Well, I think that’s a very important question, Keith. There are new parts of the definition for myeloma that need to be really emphasized. It used to be a disease defined by symptoms with the old CRAB criteria. Patients used to have either hypoglycemia, renal failure, anemia, or bone lesions, and typically that manifested with symptoms. But with the new definition, we have biomarkers of those to make the diagnosis. And the three biomarkers that are part of the criteria include light chains in the blood. If the light chain ratio is greater than 100 and the one that’s elevated—the involved one—is more than 10 mg/dL. That would also make it a myeloma requiring therapy by guidelines.

The second one is if the plasma cell infiltration in the marrow is greater than 60%; again, multiple myeloma requiring therapy. And the third one would be if MRI is conducted of the spine and the pelvis, or for the whole body, and if two or more focal areas are found—two focal areas of the marrow or the bone. Again, this is multiple myeloma requiring therapy. So, you don’t have to have symptoms.

Keith Stewart, MD, CHB: Does it have to be an MRI? Can a PET scan do the same thing? Or a skeletal survey?

C. Ola Landgren, MD, PhD: By the new criteria, the bone lesions—as part of the CRAB criteria—could be done either by x-ray or PET-CT scan. At my institution, we have implemented PET-CT as the method of choice. So, that would focus on bone lesions. MRI would also capture changes in the marrow, while the PET-CT is not really the ideal choice.

Keith Stewart, MD, CHB: How many patients are reclassified as having myeloma based on marrow plasmacytosis, high-free light chain, and bone lesion? How many move from being smoldering to needing treatment?

C. Ola Landgren, MD, PhD: The literature is not entirely clear because the number of patients that have been worked up to address that question, I think, is still not very, very large. I think a round number is probably around 30% of patients that are previously called small-drain. They probably fall into the category of multiple myeloma requiring therapy, based on these biomarkers.

Keith Stewart, MD, CHB: So, we’re gradually moving back a little bit in who we think needs active therapy. And there was a presentation yesterday from the Mayo Clinic, Dr. Fonseca. For those patients who don’t meet criteria, but you’re following over time, what do you think of that idea? Use some pretty simple techniques, falling hemoglobin, and tell us about that.

Rafael Fonseca, MD: It was a very interesting presentation. I don’t think it’s definitive, but it’s one of the first times that we’re looking at this in a dynamic way. All of our classifications have been static. We just take a number of parameters, number of biomarkers, so we estimate a risk. But, of course, in the real world, we follow patients, and we see what happens over time, and that’s what we now call clinical judgment or criteria.

Essentially, the Mayo study looked at patients who had repeated sampling and data on smoldering myeloma. And they looked at two variables, which are obviously variables that we would be worried about: an increase in the monoclonal protein—in their case, in the study—of 0.5 or a decrease in hemoglobin by 0.5. And then if you start mixing that with some of other markers, such as plasmacytosis, in the axis of 20%, you actually are able to stratify the smoldering patients. I don’t think it’s a definitive study, but it’s certainly a very important step forward, so that, in the real world, we can adapt.

Keith Stewart, MD, CHB: It seems kind of simplistic. Isn’t it already true that when we’re following a smoldering myeloma, you see the hemoglobin drop and the protein rising, that you’re likely to start therapy at some point?

Rafael Fonseca, MD: It’s true. But it’s just a validation of what we’re seeing in the clinic. And I think it’s an objective way of saying, in fact, how you’re applying your clinical judgment does make sense. Up to this point, it’s been a badge of honor to be conservative in myeloma. We always live by the mantra: you don’t want to treat too early, but, of course, we don’t want to treat too late. And I think the studies are taking us to that point that we want to correct.

Keith Stewart, MD, CHB: I always think that you would never leave a breast cancer untreated. I always wonder, why don’t we treat all of our smoldering myelomas? Jatin, what’s the…

Jatin P. Shah, MD: It’s important, but I think it’s important to understand why we have these criteria, as well. So, the criteria that Ola laid out were very specific because they’ve identified patients who have a higher likely to progression in the next 18 to 24 months. Those are the reasons why we came up with that criteria. And if we look at other patients, they may not progress out till 9 or 10 years. And so for those patients, they may not need therapy. I think that if we can identify the subset of patients that are progressing in a very short timeframe: 12, 18, 24 months…

Keith Stewart, MD, CHB: The high-risk population?

Jatin P. Shah, MD: The high-risk population. That makes sense, now, to target those patients in particular. And just one comment about just the free-light chain ratio. Again, speaking to the dynamic process of this, you know if we look at MRI lesions or the bone marrow plasmacytosis, I think that we all feel comfortable with that. The only caveat that I have clinically is, sometimes a free-light chain ratio can go up in the setting where there is renal dysfunction or infection or vaccination. So, if your patient just had this and came in with a one-time incidence, I think it’s important if you have a low bone marrow plasmacytosis and nothing else; that if it’s only based on the free-light chain ratio, maybe to recheck that again in a few weeks if it’s due to some recent infection. Because sometimes we can see that. It could be rather volatile.

Transcript Edited for Clarity
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Transcript:

Keith Stewart, MD, CHB:
Hello, and thank you for joining us today for this OncLive Peer Exchange Panel Discussion on the topic of multiple myeloma. These are exciting times in the field of multiple myeloma research, with several new agents approved by the FDA in 2015. However, along with this unprecedented progress comes increased complexity in terms of choosing the best course of therapy for an individual patient. In this OncLive Peer Exchange, I am joined by a panel of experts in the field of myeloma. Today, we will discuss how the changes in NCCN guidelines and the introduction of new data from the ASCO 2016 meeting will affect routine clinical practice.

My name is Dr. Keith Stewart, and I’m the Vasek and Anna Maria Polak Professor of Cancer Research at the Mayo Clinic. Participating today on our distinguished panel is Dr. William Bensinger, chief of the myeloma program at the Swedish Cancer Institute in Seattle, Washington; Dr. Rafael Fonseca, a Getz Family Professor of Cancer and the chair of the Department of Medicine at the Mayo Clinic in Arizona; Dr. Ola Landgren, professor of medicine and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center in New York; and, of course, Dr. Jatin Shah, associate professor of medicine at the MD Anderson Cancer Center in Houston, Texas. Thank you for joining us, and let’s get started.

I wanted to start perhaps by talking about some changes in how we think about who actually has myeloma in the first place that may or may not require therapy. Dr. Landgren, I’m looking at you because you’ve been quite active in this field. Can you explain to the audience what’s changed recently and who we think actually has myeloma that needs therapy?

C. Ola Landgren, MD, PhD: Well, I think that’s a very important question, Keith. There are new parts of the definition for myeloma that need to be really emphasized. It used to be a disease defined by symptoms with the old CRAB criteria. Patients used to have either hypoglycemia, renal failure, anemia, or bone lesions, and typically that manifested with symptoms. But with the new definition, we have biomarkers of those to make the diagnosis. And the three biomarkers that are part of the criteria include light chains in the blood. If the light chain ratio is greater than 100 and the one that’s elevated—the involved one—is more than 10 mg/dL. That would also make it a myeloma requiring therapy by guidelines.

The second one is if the plasma cell infiltration in the marrow is greater than 60%; again, multiple myeloma requiring therapy. And the third one would be if MRI is conducted of the spine and the pelvis, or for the whole body, and if two or more focal areas are found—two focal areas of the marrow or the bone. Again, this is multiple myeloma requiring therapy. So, you don’t have to have symptoms.

Keith Stewart, MD, CHB: Does it have to be an MRI? Can a PET scan do the same thing? Or a skeletal survey?

C. Ola Landgren, MD, PhD: By the new criteria, the bone lesions—as part of the CRAB criteria—could be done either by x-ray or PET-CT scan. At my institution, we have implemented PET-CT as the method of choice. So, that would focus on bone lesions. MRI would also capture changes in the marrow, while the PET-CT is not really the ideal choice.

Keith Stewart, MD, CHB: How many patients are reclassified as having myeloma based on marrow plasmacytosis, high-free light chain, and bone lesion? How many move from being smoldering to needing treatment?

C. Ola Landgren, MD, PhD: The literature is not entirely clear because the number of patients that have been worked up to address that question, I think, is still not very, very large. I think a round number is probably around 30% of patients that are previously called small-drain. They probably fall into the category of multiple myeloma requiring therapy, based on these biomarkers.

Keith Stewart, MD, CHB: So, we’re gradually moving back a little bit in who we think needs active therapy. And there was a presentation yesterday from the Mayo Clinic, Dr. Fonseca. For those patients who don’t meet criteria, but you’re following over time, what do you think of that idea? Use some pretty simple techniques, falling hemoglobin, and tell us about that.

Rafael Fonseca, MD: It was a very interesting presentation. I don’t think it’s definitive, but it’s one of the first times that we’re looking at this in a dynamic way. All of our classifications have been static. We just take a number of parameters, number of biomarkers, so we estimate a risk. But, of course, in the real world, we follow patients, and we see what happens over time, and that’s what we now call clinical judgment or criteria.

Essentially, the Mayo study looked at patients who had repeated sampling and data on smoldering myeloma. And they looked at two variables, which are obviously variables that we would be worried about: an increase in the monoclonal protein—in their case, in the study—of 0.5 or a decrease in hemoglobin by 0.5. And then if you start mixing that with some of other markers, such as plasmacytosis, in the axis of 20%, you actually are able to stratify the smoldering patients. I don’t think it’s a definitive study, but it’s certainly a very important step forward, so that, in the real world, we can adapt.

Keith Stewart, MD, CHB: It seems kind of simplistic. Isn’t it already true that when we’re following a smoldering myeloma, you see the hemoglobin drop and the protein rising, that you’re likely to start therapy at some point?

Rafael Fonseca, MD: It’s true. But it’s just a validation of what we’re seeing in the clinic. And I think it’s an objective way of saying, in fact, how you’re applying your clinical judgment does make sense. Up to this point, it’s been a badge of honor to be conservative in myeloma. We always live by the mantra: you don’t want to treat too early, but, of course, we don’t want to treat too late. And I think the studies are taking us to that point that we want to correct.

Keith Stewart, MD, CHB: I always think that you would never leave a breast cancer untreated. I always wonder, why don’t we treat all of our smoldering myelomas? Jatin, what’s the…

Jatin P. Shah, MD: It’s important, but I think it’s important to understand why we have these criteria, as well. So, the criteria that Ola laid out were very specific because they’ve identified patients who have a higher likely to progression in the next 18 to 24 months. Those are the reasons why we came up with that criteria. And if we look at other patients, they may not progress out till 9 or 10 years. And so for those patients, they may not need therapy. I think that if we can identify the subset of patients that are progressing in a very short timeframe: 12, 18, 24 months…

Keith Stewart, MD, CHB: The high-risk population?

Jatin P. Shah, MD: The high-risk population. That makes sense, now, to target those patients in particular. And just one comment about just the free-light chain ratio. Again, speaking to the dynamic process of this, you know if we look at MRI lesions or the bone marrow plasmacytosis, I think that we all feel comfortable with that. The only caveat that I have clinically is, sometimes a free-light chain ratio can go up in the setting where there is renal dysfunction or infection or vaccination. So, if your patient just had this and came in with a one-time incidence, I think it’s important if you have a low bone marrow plasmacytosis and nothing else; that if it’s only based on the free-light chain ratio, maybe to recheck that again in a few weeks if it’s due to some recent infection. Because sometimes we can see that. It could be rather volatile.

Transcript Edited for Clarity
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