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Classifying Indolent Versus Active Myeloma

Panelists: Keith Stewart, MB, CHB, Mayo Clinic; Sagar Lonial, MD, Winship Cancer Institute; Paul Richardson, MD, Dana-Farber Cancer Institute; Amrita Krishnan, MD, City of Hope Comprehensive Cancer Center; Saad Usmani, MD, Levine Cancer Institute
Published: Tuesday, Jan 17, 2017



Transcript:

Keith Stewart, MB, CHB:
Hello, and thank you for joining us today for this OncLive Peer Exchange® on the topic of “Treatment of Multiple Myeloma in 2017 and Beyond.” As we continue to experience unprecedented progress in the field of multiple myeloma research, treating patients has become increasingly complex. Because of this complexity, evidence-based management of patients involves an “Art of Medicine” approach. In this OncLive Peer Exchange®, a panel of world-renowned experts will join me to discuss how the latest science can be incorporated into the practical management of myeloma in 2017 and beyond.

My name is Dr. Keith Stewart, and I am a Vasek and Anna Maria Polak professor of cancer research at the Mayo Clinic in Scottsdale, Arizona. Participating today on our distinguished panel are: Dr. Amrita Krishnan, director of the Multiple Myeloma Program for the City of Hope Comprehensive Cancer Center in Duarte, California; Dr. Sagar Lonial, professor and chair of the Department of Hematology and Medical Oncology and chief medical officer at the Winship Cancer Institute Emory University School of Medicine in Atlanta; Dr. Paul Richardson, clinical program leader and director of clinical research for the Jerome Lipper Multiple Myeloma Center and the R.J. Corman professor of medicine at the Dana-Farber Cancer Institute, Harvard Medical School; and Dr. Saad Usmani, chief of the Plasma Cell Disorders Program and clinical professor, Department of Hematology, Oncology, and Blood Disorders at the Levine Cancer Institute, Carolinas Healthcare System. Thank you, all, for joining us and let’s get started.

First of all, we’re going to talk a little bit about the classification of early myeloma and what constitutes indolent versus active disease. There have been some changes in the way we approach that over the past 1 to 2 years. Dr. Lonial, do you want to start us out?

Sagar Lonial, MD: Yes. I think about 18 months ago, the Myeloma Work Group redefined what it means to be symptomatic myeloma versus smoldering. A lot of this came up because of concerns of patients, with rapid time to progression, being categorized as “smoldering” and observed. And so, in addition to the traditional CRAB criteria that we have used for decades, we added 3 new criteria, and this includes greater than 60% plasma cells in the marrow, free light chain ratio greater than 100, or an MRI with greater than 1 focal lesion seen on the study.

Keith Stewart, MB, CHB: And those patients you would now constitute as active disease and start treatment.

Sagar Lonial, MD: Yes. Basically, those are patients who had an 80% risk of progression to symptomatic myeloma within 2 years, and there’s no reason to wait on those patients. I think the other piece about those guidelines is that the use of skeletal surveys alone, in the context of patients who may be MGUS (monoclonal gammopathy of undetermined significance) or smoldering, is no longer considered standard, and patients need to have more advanced imaging, whether it’s an MRI or a PET scan.

Keith Stewart, MB, CHB: Since you brought that topic up of imaging, let’s turn our attention to that. Paul, tell us about what’s known and what has been known because the recent studies looked at PET and MRI scanning in newly-diagnosed myeloma. Tell us about those.

Paul Richardson, MD: Well, thank you, Keith. I think I would completely agree with Sagar, that the role of advanced imaging in this setting is now clearly established as a new standard of care to enhance our ability to primarily detect early bone disease. And, I think, certainly, in that regard, the use of both MRI and PET/CT is clearly warranted. We’ve had a number of trials that have looked in various different settings at the value of advanced imaging, and clearly they’ve been useful.

Keith Stewart, MB, CHB: Which one would you recommend? What do you do in your practice?

Paul Richardson, MD: I frankly still use skeletal survey, but I augment it with PET/CT when clinically appropriate, and we use MRI. And as part of our protocol-directed approaches in smoldering disease, we usually use all 3.

Keith Stewart, MB, CHB: Now, I think the French and your group have been doing a study where you do PET and MRI scanning. If I recall correctly, there was some evidence that that could be predictive for outcomes once you start treatment?

Paul Richardson, MD: Yes. In the context of active disease, the imaging part of the study has been actually led by our French colleagues. Primarily, in that setting, they’ve been able to demonstrate that it adds a level of sensitivity to MRD assessment, minimal residual disease assessment, that actually correlates with outcome. So, we have the concept of MRD assessment, including imaging.

Keith Stewart, MB, CHB: Amrita, what other tests need to be done on a patient that we’re working up that help risk stratify patients?

Amrita Krishnan, MD: Well, I think, certainly, we can’t ignore the role of cytogenetics and the biology of each person’s myeloma. And I think your group has done a lot of work in terms of personalized medicine. We’re going to get even more sophisticated about that, and really being able to predict who is going to have more biologically aggressive disease.

Keith Stewart, MB, CHB: So, if you’re in community practice, what do you think is the minimum level of testing that should be performed?

Amrita Krishnan, MD: I think targeted FISH analysis is really widely available. And, again, I think it’s important that people know their lab, and that they are truly doing targeted FISH on the plasma cells, so that they’re comfortable with those results.

Keith Stewart, MB, CHB: Are there any specific indicators that would send warning signals to the physician that they should be aware of?

Amrita Krishnan, MD: I think there are things that we traditionally consider high-risk cytogenetics, for example, 17p deletion certainly would be one that would be cause to think about. In a patient that you still think is asymptomatic, you would certainly have a higher degree of closer monitoring.

Keith Stewart, MB, CHB: How about the LDH, is that something you use?

Amrita Krishnan, MD: I do use it. I’m not sure that in very early stages of disease it would be as useful, but I think it’s an easy, widely available test that you can certainly follow. And, certainly, changes in that would be a quick, easy marker to warrant further work-up.

Keith Stewart, MB, CHB: So, it sounds that we’re beginning to think about treating myeloma patients a bit earlier in the course, slowly defining those who are going to progress quickly. Do you treat smoldering myeloma, Saad? What’s your approach to that?

Saad Usmani, MD: Generally, we like to follow the Mayo Clinic Risk Criteria.

Keith Stewart, MB, CHB: Very wise.

Saad Usmani, MD: I knew you would say that. For the low-risk smoldering myeloma patients, they essentially need to be followed very similarly to the MGUS folks, so maybe checking their labs once a year and following them.

Keith Stewart, MB, CHB: Just for the audience, low risk being what? Tell me what low risk looks like?

Saad Usmani, MD: It has to do with the criteria around M-spike being 3 g or higher, bone marrow plasma cytosis being 20% or above, and I think the light chain has to be abnormal, involved versus uninvolved over 10, if I remember correctly.

Sagar Lonial, MD: Greater than 8.

Saad Usmani, MD: There are several criteria. There are, the last time I checked, 11 different ones, including the Spanish Myeloma Criteria, which includes the immunophenotypic flow abnormalities, the aberration of 95% or more. But, I think for community doctors out there, it’s probably still the Mayo Clinic Criteria. The low- and intermediate-risk folks still probably need to be followed just with labs. Maybe the intermediate folks need to be followed twice a year with labs.

Transcript Edited for Clarity

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Transcript:

Keith Stewart, MB, CHB:
Hello, and thank you for joining us today for this OncLive Peer Exchange® on the topic of “Treatment of Multiple Myeloma in 2017 and Beyond.” As we continue to experience unprecedented progress in the field of multiple myeloma research, treating patients has become increasingly complex. Because of this complexity, evidence-based management of patients involves an “Art of Medicine” approach. In this OncLive Peer Exchange®, a panel of world-renowned experts will join me to discuss how the latest science can be incorporated into the practical management of myeloma in 2017 and beyond.

My name is Dr. Keith Stewart, and I am a Vasek and Anna Maria Polak professor of cancer research at the Mayo Clinic in Scottsdale, Arizona. Participating today on our distinguished panel are: Dr. Amrita Krishnan, director of the Multiple Myeloma Program for the City of Hope Comprehensive Cancer Center in Duarte, California; Dr. Sagar Lonial, professor and chair of the Department of Hematology and Medical Oncology and chief medical officer at the Winship Cancer Institute Emory University School of Medicine in Atlanta; Dr. Paul Richardson, clinical program leader and director of clinical research for the Jerome Lipper Multiple Myeloma Center and the R.J. Corman professor of medicine at the Dana-Farber Cancer Institute, Harvard Medical School; and Dr. Saad Usmani, chief of the Plasma Cell Disorders Program and clinical professor, Department of Hematology, Oncology, and Blood Disorders at the Levine Cancer Institute, Carolinas Healthcare System. Thank you, all, for joining us and let’s get started.

First of all, we’re going to talk a little bit about the classification of early myeloma and what constitutes indolent versus active disease. There have been some changes in the way we approach that over the past 1 to 2 years. Dr. Lonial, do you want to start us out?

Sagar Lonial, MD: Yes. I think about 18 months ago, the Myeloma Work Group redefined what it means to be symptomatic myeloma versus smoldering. A lot of this came up because of concerns of patients, with rapid time to progression, being categorized as “smoldering” and observed. And so, in addition to the traditional CRAB criteria that we have used for decades, we added 3 new criteria, and this includes greater than 60% plasma cells in the marrow, free light chain ratio greater than 100, or an MRI with greater than 1 focal lesion seen on the study.

Keith Stewart, MB, CHB: And those patients you would now constitute as active disease and start treatment.

Sagar Lonial, MD: Yes. Basically, those are patients who had an 80% risk of progression to symptomatic myeloma within 2 years, and there’s no reason to wait on those patients. I think the other piece about those guidelines is that the use of skeletal surveys alone, in the context of patients who may be MGUS (monoclonal gammopathy of undetermined significance) or smoldering, is no longer considered standard, and patients need to have more advanced imaging, whether it’s an MRI or a PET scan.

Keith Stewart, MB, CHB: Since you brought that topic up of imaging, let’s turn our attention to that. Paul, tell us about what’s known and what has been known because the recent studies looked at PET and MRI scanning in newly-diagnosed myeloma. Tell us about those.

Paul Richardson, MD: Well, thank you, Keith. I think I would completely agree with Sagar, that the role of advanced imaging in this setting is now clearly established as a new standard of care to enhance our ability to primarily detect early bone disease. And, I think, certainly, in that regard, the use of both MRI and PET/CT is clearly warranted. We’ve had a number of trials that have looked in various different settings at the value of advanced imaging, and clearly they’ve been useful.

Keith Stewart, MB, CHB: Which one would you recommend? What do you do in your practice?

Paul Richardson, MD: I frankly still use skeletal survey, but I augment it with PET/CT when clinically appropriate, and we use MRI. And as part of our protocol-directed approaches in smoldering disease, we usually use all 3.

Keith Stewart, MB, CHB: Now, I think the French and your group have been doing a study where you do PET and MRI scanning. If I recall correctly, there was some evidence that that could be predictive for outcomes once you start treatment?

Paul Richardson, MD: Yes. In the context of active disease, the imaging part of the study has been actually led by our French colleagues. Primarily, in that setting, they’ve been able to demonstrate that it adds a level of sensitivity to MRD assessment, minimal residual disease assessment, that actually correlates with outcome. So, we have the concept of MRD assessment, including imaging.

Keith Stewart, MB, CHB: Amrita, what other tests need to be done on a patient that we’re working up that help risk stratify patients?

Amrita Krishnan, MD: Well, I think, certainly, we can’t ignore the role of cytogenetics and the biology of each person’s myeloma. And I think your group has done a lot of work in terms of personalized medicine. We’re going to get even more sophisticated about that, and really being able to predict who is going to have more biologically aggressive disease.

Keith Stewart, MB, CHB: So, if you’re in community practice, what do you think is the minimum level of testing that should be performed?

Amrita Krishnan, MD: I think targeted FISH analysis is really widely available. And, again, I think it’s important that people know their lab, and that they are truly doing targeted FISH on the plasma cells, so that they’re comfortable with those results.

Keith Stewart, MB, CHB: Are there any specific indicators that would send warning signals to the physician that they should be aware of?

Amrita Krishnan, MD: I think there are things that we traditionally consider high-risk cytogenetics, for example, 17p deletion certainly would be one that would be cause to think about. In a patient that you still think is asymptomatic, you would certainly have a higher degree of closer monitoring.

Keith Stewart, MB, CHB: How about the LDH, is that something you use?

Amrita Krishnan, MD: I do use it. I’m not sure that in very early stages of disease it would be as useful, but I think it’s an easy, widely available test that you can certainly follow. And, certainly, changes in that would be a quick, easy marker to warrant further work-up.

Keith Stewart, MB, CHB: So, it sounds that we’re beginning to think about treating myeloma patients a bit earlier in the course, slowly defining those who are going to progress quickly. Do you treat smoldering myeloma, Saad? What’s your approach to that?

Saad Usmani, MD: Generally, we like to follow the Mayo Clinic Risk Criteria.

Keith Stewart, MB, CHB: Very wise.

Saad Usmani, MD: I knew you would say that. For the low-risk smoldering myeloma patients, they essentially need to be followed very similarly to the MGUS folks, so maybe checking their labs once a year and following them.

Keith Stewart, MB, CHB: Just for the audience, low risk being what? Tell me what low risk looks like?

Saad Usmani, MD: It has to do with the criteria around M-spike being 3 g or higher, bone marrow plasma cytosis being 20% or above, and I think the light chain has to be abnormal, involved versus uninvolved over 10, if I remember correctly.

Sagar Lonial, MD: Greater than 8.

Saad Usmani, MD: There are several criteria. There are, the last time I checked, 11 different ones, including the Spanish Myeloma Criteria, which includes the immunophenotypic flow abnormalities, the aberration of 95% or more. But, I think for community doctors out there, it’s probably still the Mayo Clinic Criteria. The low- and intermediate-risk folks still probably need to be followed just with labs. Maybe the intermediate folks need to be followed twice a year with labs.

Transcript Edited for Clarity
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