In Conversation: Ola Landgren on Updated Myeloma Definition
Dr Abutalib: I would like to start by clarifying the role of whole-body MRI (WB-MRI) as a diagnostic test. How important is this test to rule out smoldering multiple myeloma (SMM)?
Dr Landgren: In the new updated 2014 IMWG criteria, in addition to the conventional CRAB criteria—hypercalcemia, renal failure, anemia, and lytic bone lesions—there are three more criteria: involved/uninvolved serum free light-chain ratio ≥ 100; bone marrow plasma cells (BMPCs) ≥ 60%; and two or more focal bony lesions > 5 mm on MRI.
The role of MRI in plasma cell disorders originates from a retrospective German study using WB-MRI in a series of 149 patients with SMM. They found that focal lesions were detectable in 28% of patients. The presence of two or more focal lesions on MRI was associated with an increased risk for progression to symptomatic myeloma.
This study prompted the Greek Myeloma Group to review their database. They had information on 67 patients with SMM assessed by spine MRI at diagnosis and a minimum of 2.5 years of follow-up. These two studies are referenced in the original IMWG paper published in Lancet Oncology.
That is how I use whole-body MRI in patients who are otherwise asymptomatic—to make sure that they don't fulfill the myeloma diagnosis per the new updated 2014 IMWG criteria.
Dr Abutalib: Bone imaging with MRI is an exhaustive test, if you look from the perspective of whole-body MRI. Do you suggest MRI of a specific area, such as the spine, or truly whole-body MRI?
Dr Landgren: Access to tests varies across continents and within countries. At our institution, we do a whole-body MRI. For institutions that don't have access to whole-body MRI, on the basis of available information, MRI of the spine is the second best option. Either whole-body MRI or MRI of the spine is recommended by the IMWG criteria.
In the small study by the Greek Myeloma Group, they argue that about 15% of patients with SMM present with focal lesions on spine MRI. At the same time, they acknowledge that MRI of the spine may miss extra-axial skeletal focal lesions, which in the German study were present in 10% of the SMM patients who had a normal spine MRI (vs 17% of patients with abnormal spine MRI). Thus, about one half the patients with extra-axial skeletal focal lesions detectable with whole-body MRI they were not captured with a spine MRI. Furthermore, as pointed out by the Greek Myeloma Group, MRI of the spine is less time-consuming and causes less discomfort to the patient, costs less than whole-body MRI, and is widely available.
I wanted to give these additional perspectives. As I already said, at our institution, we prefer whole-body MRI because it is more sensitive.
Dr Abutalib: Just to summarize, in a patient who meets the criteria for SMM outside of imaging, you will proceed not with a skeletal survey at your institution, but a whole-body MRI, and in future with whole-body PET/MRI?
Dr Landgren: First of all, to rule out bone lesions, either a skeletal survey or a PET/CT are the two main options. At our institution, we prefer PET/CT because it is over 30 times more sensitive in terms of capturing lytic bone lesions. The new IMWG guidelines state that lytic lesions > 5 mm, detected either by skeletal survey or PET/CT, meet the criteria for multiple myeloma requiring therapy. For institutions that do not have access to PET/CT, skeletal survey is the second best option.
When it comes to ruling out focal lesions in the bone marrow, we do WB-MRI, as we just discussed.
On a practical note, if a patient has clear evidence of lytic bone lesions detectable on PET/CT, there may not be an emerging need to do WB-MRI for the purpose of establishing the diagnosis. On a case-by-case basis, sometimes we do and sometimes we don't do WB-MRI in these situations.
Dr Abutalib: And the reason for that choice seems obvious, but what are the data against skeletal survey?
Dr Landgren: We and others have done studies to confirm these findings. If you do skeletal survey and you diagnose patients as having SMM, and then you do PET/CT, around 30% of those patients have lytic lesions that were otherwise negative for bone lesions. These data are submitted and are currently under review.
Dr Abutalib: What about low-dose CT or, for practical reasons, PET/CT?
Dr Landgren: Typically, and in the guidelines, we have said that you should look for lytic bone lesions. The old guidelines relied on the old skeletal survey; in the new guidelines, we said that with PET/CT, the CT component has a higher detection rate than skeletal survey for bone lesions. It clearly says in these new guidelines that the intent from the early versions was that one should interpret these lesions with CT as lytic lesions. That was very confusing to many clinicians in the past.
Does it matter or does it not matter? The answer is, yes it does, and CT is more sensitive than skeletal survey, so at our institution we have virtually replaced the use of skeletal surveys with the use of low-dose CT. We do it for practical purposes as PET/CT, and the low-dose CT is part of the PET/CT.
Bone Imaging in the Diagnosis of Plasma Cell Disorders
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Syed A. Abutalib, MD |
Dr Abutalib: I would like to start by clarifying the role of whole-body MRI (WB-MRI) as a diagnostic test. How important is this test to rule out smoldering multiple myeloma (SMM)?
Dr Landgren: In the new updated 2014 IMWG criteria, in addition to the conventional CRAB criteria—hypercalcemia, renal failure, anemia, and lytic bone lesions—there are three more criteria: involved/uninvolved serum free light-chain ratio ≥ 100; bone marrow plasma cells (BMPCs) ≥ 60%; and two or more focal bony lesions > 5 mm on MRI.
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Carl Ola Landgren, MD, PhD |
The role of MRI in plasma cell disorders originates from a retrospective German study using WB-MRI in a series of 149 patients with SMM. They found that focal lesions were detectable in 28% of patients. The presence of two or more focal lesions on MRI was associated with an increased risk for progression to symptomatic myeloma.
This study prompted the Greek Myeloma Group to review their database. They had information on 67 patients with SMM assessed by spine MRI at diagnosis and a minimum of 2.5 years of follow-up. These two studies are referenced in the original IMWG paper published in Lancet Oncology.
That is how I use whole-body MRI in patients who are otherwise asymptomatic—to make sure that they don't fulfill the myeloma diagnosis per the new updated 2014 IMWG criteria.
Dr Abutalib: Bone imaging with MRI is an exhaustive test, if you look from the perspective of whole-body MRI. Do you suggest MRI of a specific area, such as the spine, or truly whole-body MRI?
Dr Landgren: Access to tests varies across continents and within countries. At our institution, we do a whole-body MRI. For institutions that don't have access to whole-body MRI, on the basis of available information, MRI of the spine is the second best option. Either whole-body MRI or MRI of the spine is recommended by the IMWG criteria.
In the small study by the Greek Myeloma Group, they argue that about 15% of patients with SMM present with focal lesions on spine MRI. At the same time, they acknowledge that MRI of the spine may miss extra-axial skeletal focal lesions, which in the German study were present in 10% of the SMM patients who had a normal spine MRI (vs 17% of patients with abnormal spine MRI). Thus, about one half the patients with extra-axial skeletal focal lesions detectable with whole-body MRI they were not captured with a spine MRI. Furthermore, as pointed out by the Greek Myeloma Group, MRI of the spine is less time-consuming and causes less discomfort to the patient, costs less than whole-body MRI, and is widely available.
I wanted to give these additional perspectives. As I already said, at our institution, we prefer whole-body MRI because it is more sensitive.
Dr Abutalib: Just to summarize, in a patient who meets the criteria for SMM outside of imaging, you will proceed not with a skeletal survey at your institution, but a whole-body MRI, and in future with whole-body PET/MRI?
Dr Landgren: First of all, to rule out bone lesions, either a skeletal survey or a PET/CT are the two main options. At our institution, we prefer PET/CT because it is over 30 times more sensitive in terms of capturing lytic bone lesions. The new IMWG guidelines state that lytic lesions > 5 mm, detected either by skeletal survey or PET/CT, meet the criteria for multiple myeloma requiring therapy. For institutions that do not have access to PET/CT, skeletal survey is the second best option.
When it comes to ruling out focal lesions in the bone marrow, we do WB-MRI, as we just discussed.
On a practical note, if a patient has clear evidence of lytic bone lesions detectable on PET/CT, there may not be an emerging need to do WB-MRI for the purpose of establishing the diagnosis. On a case-by-case basis, sometimes we do and sometimes we don't do WB-MRI in these situations.
Dr Abutalib: And the reason for that choice seems obvious, but what are the data against skeletal survey?
Dr Landgren: We and others have done studies to confirm these findings. If you do skeletal survey and you diagnose patients as having SMM, and then you do PET/CT, around 30% of those patients have lytic lesions that were otherwise negative for bone lesions. These data are submitted and are currently under review.
Dr Abutalib: What about low-dose CT or, for practical reasons, PET/CT?
Dr Landgren: Typically, and in the guidelines, we have said that you should look for lytic bone lesions. The old guidelines relied on the old skeletal survey; in the new guidelines, we said that with PET/CT, the CT component has a higher detection rate than skeletal survey for bone lesions. It clearly says in these new guidelines that the intent from the early versions was that one should interpret these lesions with CT as lytic lesions. That was very confusing to many clinicians in the past.
Does it matter or does it not matter? The answer is, yes it does, and CT is more sensitive than skeletal survey, so at our institution we have virtually replaced the use of skeletal surveys with the use of low-dose CT. We do it for practical purposes as PET/CT, and the low-dose CT is part of the PET/CT.
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