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Have you had minimal residual disease testing done?
I am wondering how many people have had minimal residual disease (MRD) testing done? What test was done? How long have you been in remission?
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blair77 - Who do you know with myeloma?: My husband
- When were you/they diagnosed?: April 2013
- Age at diagnosis: 43
Re: Have you had minimal residual disease testing done?
Good question, blair77. I'll be interested in what other say.
I had MRD testing done by flow cytometry in July. At the same time I was told that I'd achieved sCR, moving to that from VGPR. In October lab results, my FLC kappa/lambda ratio is slightly high, so I think that takes me out of the stringent part of sCR, so I guess I am just CR now.
I am in a clinical trial, so I think the MRD testing was done as part of that. I'm not sure if they would have done it were I not in the trial. However, I have been told that MRD testing will be done regularly at the center that I go to; I'm just not sure if they have started that practice yet.
I had MRD testing done by flow cytometry in July. At the same time I was told that I'd achieved sCR, moving to that from VGPR. In October lab results, my FLC kappa/lambda ratio is slightly high, so I think that takes me out of the stringent part of sCR, so I guess I am just CR now.
I am in a clinical trial, so I think the MRD testing was done as part of that. I'm not sure if they would have done it were I not in the trial. However, I have been told that MRD testing will be done regularly at the center that I go to; I'm just not sure if they have started that practice yet.
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mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Have you had minimal residual disease testing done?
Hi Mikeb,
Do you know if you were considered MRD negative or MRD positive? As I understand, you can be in sCR and still be MRD positive.
Do you know if you were considered MRD negative or MRD positive? As I understand, you can be in sCR and still be MRD positive.
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blair77 - Who do you know with myeloma?: My husband
- When were you/they diagnosed?: April 2013
- Age at diagnosis: 43
Re: Have you had minimal residual disease testing done?
Blair,
To a layman like me, the term "MRD" has unfortunately gotten muddled in the field of multiple myeloma ... at least in my mind.
If you are talking about the new low-cost "MRD-Zero" 8-color flow cytometry test that hat has been developed by the Black Swan Initiative, my understanding is that only a couple of facilities currently have that specific flow test up and running (although many institutes utilize other types of non-standardized flow testing). Hopefully, that standardized test will be rolled out to a lot more facilities in the near future. Note that I'm not a fan of the "MRD-Zero" name since the test really doesn't ensure that one has "zero" MRD. But it will still be good to have a standardized, low-cost test out on the market.
There are also other types of MRD testing for multiple myeloma that are being explored that include Next Generation Sequencing (NGS) and polymerase chain reaction (PCR) approaches.
To some extent, getting a PET/CT can also be considered a type of MRD testing.
There are pros and cons to all of the above approaches, which I won't go into here.
When I got my BMB, doing a flow cytometry test (it was a 4-color test, as I recall) was part of the battery of tests that were done on my sample. So, I've already had one type of MRD testing done.
And, yes, one could be in sCR and still be MRD positive, depending on the MRD test that was used.
To a layman like me, the term "MRD" has unfortunately gotten muddled in the field of multiple myeloma ... at least in my mind.
If you are talking about the new low-cost "MRD-Zero" 8-color flow cytometry test that hat has been developed by the Black Swan Initiative, my understanding is that only a couple of facilities currently have that specific flow test up and running (although many institutes utilize other types of non-standardized flow testing). Hopefully, that standardized test will be rolled out to a lot more facilities in the near future. Note that I'm not a fan of the "MRD-Zero" name since the test really doesn't ensure that one has "zero" MRD. But it will still be good to have a standardized, low-cost test out on the market.
There are also other types of MRD testing for multiple myeloma that are being explored that include Next Generation Sequencing (NGS) and polymerase chain reaction (PCR) approaches.
To some extent, getting a PET/CT can also be considered a type of MRD testing.
There are pros and cons to all of the above approaches, which I won't go into here.
When I got my BMB, doing a flow cytometry test (it was a 4-color test, as I recall) was part of the battery of tests that were done on my sample. So, I've already had one type of MRD testing done.
And, yes, one could be in sCR and still be MRD positive, depending on the MRD test that was used.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Have you had minimal residual disease testing done?
Hi Blair77,
Multibilly, as usual, makes some very good points. By your asking these questions, I was assuming you are trying to understand some of the differences between the different versions of MRD testing. But it's good that Multibilly was more specific about these differences in his response.
As I understand it, my MRD testing was done with the 8-color flow cytometry test that the Black Swan initiative is trying to standardize. My myeloma center (Memorial Sloan Kettering) is one of the facilities pushing for this standardization.
I strongly agree with Multibilly's dislike of the term "MRD-Zero" for the reason he cited. Although (happily) I tested as MRD negative, my myeloma specialist emphasized to me that "the working assumption is that you still have myeloma cells in you." So we are continuing the Revlimid maintenance that I have been on.
Multibilly, as usual, makes some very good points. By your asking these questions, I was assuming you are trying to understand some of the differences between the different versions of MRD testing. But it's good that Multibilly was more specific about these differences in his response.
As I understand it, my MRD testing was done with the 8-color flow cytometry test that the Black Swan initiative is trying to standardize. My myeloma center (Memorial Sloan Kettering) is one of the facilities pushing for this standardization.
I strongly agree with Multibilly's dislike of the term "MRD-Zero" for the reason he cited. Although (happily) I tested as MRD negative, my myeloma specialist emphasized to me that "the working assumption is that you still have myeloma cells in you." So we are continuing the Revlimid maintenance that I have been on.
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mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Have you had minimal residual disease testing done?
Thanks for the information!
My husband's doctor is doing the testing with something called "clonosight." I believe it to be DNA based. He is Dr. Wolf at UCSF and has said he doesn't really yet know what the long-term implications of testing negative means.
We are using it to make a choice about staying on Revlimid maintenance.
My husband's doctor is doing the testing with something called "clonosight." I believe it to be DNA based. He is Dr. Wolf at UCSF and has said he doesn't really yet know what the long-term implications of testing negative means.
We are using it to make a choice about staying on Revlimid maintenance.
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blair77 - Who do you know with myeloma?: My husband
- When were you/they diagnosed?: April 2013
- Age at diagnosis: 43
Re: Have you had minimal residual disease testing done?
Hey Blair,
"Clonosight" is one form of the NGS approach I mentioned above. In a nut, the proprietary Clonosight method sequences the DNA of a known cancerous sample in the patient (think of this like generating a unique signature of the patient's multiple myeloma cancer). They then look for that specific patient's cancer signature in follow-up samples as part of the MRD testing process.
Is the Clonosight testing part of a clinical trial or is UCSF covering the cost of the testing? If not, my only caution would be to make sure that your insurance covers it, as I'm guessing it might not be a cheap date and that kind of testing may not yet be approved by your insurance (but I don't know that for sure).
"Clonosight" is one form of the NGS approach I mentioned above. In a nut, the proprietary Clonosight method sequences the DNA of a known cancerous sample in the patient (think of this like generating a unique signature of the patient's multiple myeloma cancer). They then look for that specific patient's cancer signature in follow-up samples as part of the MRD testing process.
Is the Clonosight testing part of a clinical trial or is UCSF covering the cost of the testing? If not, my only caution would be to make sure that your insurance covers it, as I'm guessing it might not be a cheap date and that kind of testing may not yet be approved by your insurance (but I don't know that for sure).
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Have you had minimal residual disease testing done?
Great discussion.
I am aware of one study that compared NGS to flow. The patients that were MRD negative by NGS had a significantly longer time to tumor progression (TTP) than those that were MRD positive. Here is the reference and abstract.
J Martinez-Lopez, "Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma," Blood, May 15, 2014 (open access PubMed edition)
Abstract:
We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma (multiple myeloma) patients using a sequencing-based platform in bone marrow samples from 133 multiple myeloma patients in at least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR).
The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD(-) by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P < .0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD(+).
When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10(-3) 27 months, MRD 10(-3) to 10(-5) 48 months, and MRD <10(-5) 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD(+).
In complete response patients, the TTP remained significantly longer for MRD(-) compared with MRD(+) patients (131 vs 35 months; P = .0009)."
I would be curious what the cost of the Clonosight test is. I am monitored by ASO-PCR. So far all the bills have been paid. I checked the bills that mentioned the term "molecular testing" after my one year post allo restaging. The bills totaled around $11,000. My insurance company did not pay the full amount, they paid a negotiated rate.
I am aware of one study that compared NGS to flow. The patients that were MRD negative by NGS had a significantly longer time to tumor progression (TTP) than those that were MRD positive. Here is the reference and abstract.
J Martinez-Lopez, "Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma," Blood, May 15, 2014 (open access PubMed edition)
Abstract:
We assessed the prognostic value of minimal residual disease (MRD) detection in multiple myeloma (multiple myeloma) patients using a sequencing-based platform in bone marrow samples from 133 multiple myeloma patients in at least very good partial response (VGPR) after front-line therapy. Deep sequencing was carried out in patients in whom a high-frequency myeloma clone was identified and MRD was assessed using the IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multiparametric flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR).
The applicability of deep sequencing was 91%. Concordance between sequencing and MFC and ASO-PCR was 83% and 85%, respectively. Patients who were MRD(-) by sequencing had a significantly longer time to tumor progression (TTP) (median 80 vs 31 months; P < .0001) and overall survival (median not reached vs 81 months; P = .02), compared with patients who were MRD(+).
When stratifying patients by different levels of MRD, the respective TTP medians were: MRD ≥10(-3) 27 months, MRD 10(-3) to 10(-5) 48 months, and MRD <10(-5) 80 months (P = .003 to .0001). Ninety-two percent of VGPR patients were MRD(+).
In complete response patients, the TTP remained significantly longer for MRD(-) compared with MRD(+) patients (131 vs 35 months; P = .0009)."
I would be curious what the cost of the Clonosight test is. I am monitored by ASO-PCR. So far all the bills have been paid. I checked the bills that mentioned the term "molecular testing" after my one year post allo restaging. The bills totaled around $11,000. My insurance company did not pay the full amount, they paid a negotiated rate.
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Mark11
Re: Have you had minimal residual disease testing done?
Just as an FYI ... the journal article that Mark11 referenced was summarized in a Beacon news article earlier this year. Here is the reference:
"Minimal Residual Disease, Deep Sequencing, And Prognosis In Multiple Myeloma," The Myeloma Beacon, Apr 8, 2014.
All the Beacon's articles related to minimal residual disease can be found at the MRD topic page:
Minimal residual disease - myeloma
"Minimal Residual Disease, Deep Sequencing, And Prognosis In Multiple Myeloma," The Myeloma Beacon, Apr 8, 2014.
All the Beacon's articles related to minimal residual disease can be found at the MRD topic page:
Minimal residual disease - myeloma
Re: Have you had minimal residual disease testing done?
Thanks, Beacon Staff, for the link back to the Beacon news article. It was good for me to read it again now, factoring a little more knowledge about all of this that I've gained since April.
One of the things that I've learned is that there are lots of aspects regarding the procedures used in flow cytometry testing for MRD that need to be standardized. As a couple of examples, the first bone marrow aspirate draw should always be the one used for this testing since it is likely to contain more myeloma cells (if any are present) than subsequent draws. But not all labs use this draw for MRD testing. Also, as Multibilly alluded to in an earlier comment, the number of colors used in the test makes a big difference in the test's sensitivity.
Currently, different labs use different flow cytometry procedures so it is hard to know what the test result means. As I understand it, a big part of the Black Swan initiative is to specify / standardize the procedures that should be used so that we're able to compare apples to apples when looking at flow cytometry MRD testing results. I know less about deep sequencing procedures, but imagine that there are similar procedure standardization issues there too.
This stuff is pretty complex!
One of the things that I've learned is that there are lots of aspects regarding the procedures used in flow cytometry testing for MRD that need to be standardized. As a couple of examples, the first bone marrow aspirate draw should always be the one used for this testing since it is likely to contain more myeloma cells (if any are present) than subsequent draws. But not all labs use this draw for MRD testing. Also, as Multibilly alluded to in an earlier comment, the number of colors used in the test makes a big difference in the test's sensitivity.
Currently, different labs use different flow cytometry procedures so it is hard to know what the test result means. As I understand it, a big part of the Black Swan initiative is to specify / standardize the procedures that should be used so that we're able to compare apples to apples when looking at flow cytometry MRD testing results. I know less about deep sequencing procedures, but imagine that there are similar procedure standardization issues there too.
This stuff is pretty complex!
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mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
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