There has been lots of talk about minimal residual disease recently and I also read an excellent report on this website from Dr Rajkumar.
I would like to know if anyone has been tested for MRD and what tests were involved.
Where did you get it done?
Is it only done through a clinical trial or research or can it be performed by local oncologist?
Thanks, Michelle
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Re: Minimal residual disease (MRD) testing - experiences?
Hi Michelle,
UAMS has now begun to test for MRD on at least some of their patients who have achieved a CR. I don't know if all patients are being tested for it, though.
MRD quantification is done by 8-color flow cytometric analyses of bone marrow cells. For the patients, there is nothing extra that needs to be done. The technicians just use cells obtained from the bone marrow when that procedure is done.
UAMS has now begun to test for MRD on at least some of their patients who have achieved a CR. I don't know if all patients are being tested for it, though.
MRD quantification is done by 8-color flow cytometric analyses of bone marrow cells. For the patients, there is nothing extra that needs to be done. The technicians just use cells obtained from the bone marrow when that procedure is done.
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dnalex - Name: Alex N.
- Who do you know with myeloma?: mother
- When were you/they diagnosed?: 2007
- Age at diagnosis: 56
Re: Minimal residual disease (MRD) testing - experiences?
That was indeed a great paper that Dr. Rajkumar wrote. We are very fortunate that a Thought Leader like Dr. Rajkumar takes the time to write papers for patients and that the Beacon Staff runs such a great website that Doctors are willing to write for them and educate patients. I also would like to mention Dr. Voorhees, Dr. Valent, Dr, Shain, Dr. Libby and Dr. Cohen for taking the time to answer questions here in the Forum.
I have had PCR testing done 4 times since I attained CR after my allo transplant and I have done Flow Cytometry 3 times. Generally speaking PCR is considered the more sensitive test but it must be set up for each individual patient and is expensive. PCR testing tests DNA. I looked at my last group of bills and one bill that mentioned DNA testing was for $8K and the other was for $2K. Fortunately my insurance company has been paying for them. I am not in a clinical trial but I am treated in a University setting. PCR tests cannot be setup for all patients. Flow Cytometry is not as expensive and is applicable to all patients. A recent study shows this:
"We have analyzed the applicability, sensitivity and prognostic value of allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) as a method for minimal residual disease (MRD) assessment in patients with multiple myeloma (multiple myeloma), comparing the results with those of multiparameter flow cytometry (MFC). A total of 170 patients enrolled in three consecutive Spanish trials achieving at least partial response after treatment were included. Lack of clonality detection (n=31), unsuccessful sequencing (n=17) and suboptimal ASO performance (n=51) limited the applicability of PCR to 42% of cases. MRD was finally investigated in 103 patients (including 32 previously studied) with persistent disease identified by PCR and MFC in 54% and 46% of cases, respectively. A significant correlation in MRD quantitation by both the techniques was noted (r=0.881, P<0.001), being reflective of treatment intensity. Patients with <10-4 residual tumor cells showed longer progression-free survival (PFS) compared with the rest (not reached (NR) vs 31 months, P=0.002), with similar results observed with MFC. Among complete responders (n=62), PCR discriminated two risk groups with different PFS (49 vs 26 months, P=0.001) and overall survival (NR vs 60 months, P=0.008). Thus, although less applicable than MFC, ASO RQ-PCR is a powerful technique to assess treatment efficacy and risk stratification in multiple myeloma ."
http://www.ncbi.nlm.nih.gov/pubmed/23860448
I have seen references in the literature going back to 1999 discussing the importance of a molecular response (PCR negative) in the allo transplant setting so this is not a new concept. Here is an example of Dr. Michael Cavo writing something similar to what Dr. Rajkumar wrote back in 2000:
"Persistent PCR− bone marrow samples from multiple myeloma patients in long-term CR is reminiscent of data previously reported in other malignancies.17-21 In these instances, analysis of MRD by PCR was found to closely correlate with posttransplantation clinical outcome and to provide important information for patient management. Whether this also holds true in multiple myeloma remains, as yet, unanswered. Larger molecular monitoring studies and, importantly, quantitative measures of residual tumor cells are required to further define the real value of PCR-based strategies. Results of these studies must also be compared with conventional methods of analysis to clarify the prognostic relevance of MRD detection in multiple myeloma."
"In conclusion, the data herein reported demonstrate that allo SCT induces sustained serological and molecular remission in selected patients with multiple myeloma. Although a longer follow-up is required to determine if these patients are truly cured, it is unusual for relapses to occur more than 5 years after allo BMT.'
http://bloodjournal.hematologylibrary.org/content/96/1/355.long
It seems like Doctors/Patients in the non-allo setting are discussing what the Doctors were discussing for allo patients around 13 years ago. As Dr. Rajkumar noted, LONG TERM followup (IMO 10 years minimum ) in randomized trials is needed before you can draw definitive conclusions if a therapy or response level truly correlates with a superior outcome in the majority of patients. A lot of the importance of MRD testing IMO relates to the patients thoughts. I would not be comfortable treating to anything less than a molecular CR (PCR negative). Other patients are fine with low levels of disease. Like just about everything else relating to myeloma therapy there is no right or wrong answer.
Mark
I have had PCR testing done 4 times since I attained CR after my allo transplant and I have done Flow Cytometry 3 times. Generally speaking PCR is considered the more sensitive test but it must be set up for each individual patient and is expensive. PCR testing tests DNA. I looked at my last group of bills and one bill that mentioned DNA testing was for $8K and the other was for $2K. Fortunately my insurance company has been paying for them. I am not in a clinical trial but I am treated in a University setting. PCR tests cannot be setup for all patients. Flow Cytometry is not as expensive and is applicable to all patients. A recent study shows this:
"We have analyzed the applicability, sensitivity and prognostic value of allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) as a method for minimal residual disease (MRD) assessment in patients with multiple myeloma (multiple myeloma), comparing the results with those of multiparameter flow cytometry (MFC). A total of 170 patients enrolled in three consecutive Spanish trials achieving at least partial response after treatment were included. Lack of clonality detection (n=31), unsuccessful sequencing (n=17) and suboptimal ASO performance (n=51) limited the applicability of PCR to 42% of cases. MRD was finally investigated in 103 patients (including 32 previously studied) with persistent disease identified by PCR and MFC in 54% and 46% of cases, respectively. A significant correlation in MRD quantitation by both the techniques was noted (r=0.881, P<0.001), being reflective of treatment intensity. Patients with <10-4 residual tumor cells showed longer progression-free survival (PFS) compared with the rest (not reached (NR) vs 31 months, P=0.002), with similar results observed with MFC. Among complete responders (n=62), PCR discriminated two risk groups with different PFS (49 vs 26 months, P=0.001) and overall survival (NR vs 60 months, P=0.008). Thus, although less applicable than MFC, ASO RQ-PCR is a powerful technique to assess treatment efficacy and risk stratification in multiple myeloma ."
http://www.ncbi.nlm.nih.gov/pubmed/23860448
I have seen references in the literature going back to 1999 discussing the importance of a molecular response (PCR negative) in the allo transplant setting so this is not a new concept. Here is an example of Dr. Michael Cavo writing something similar to what Dr. Rajkumar wrote back in 2000:
"Persistent PCR− bone marrow samples from multiple myeloma patients in long-term CR is reminiscent of data previously reported in other malignancies.17-21 In these instances, analysis of MRD by PCR was found to closely correlate with posttransplantation clinical outcome and to provide important information for patient management. Whether this also holds true in multiple myeloma remains, as yet, unanswered. Larger molecular monitoring studies and, importantly, quantitative measures of residual tumor cells are required to further define the real value of PCR-based strategies. Results of these studies must also be compared with conventional methods of analysis to clarify the prognostic relevance of MRD detection in multiple myeloma."
"In conclusion, the data herein reported demonstrate that allo SCT induces sustained serological and molecular remission in selected patients with multiple myeloma. Although a longer follow-up is required to determine if these patients are truly cured, it is unusual for relapses to occur more than 5 years after allo BMT.'
http://bloodjournal.hematologylibrary.org/content/96/1/355.long
It seems like Doctors/Patients in the non-allo setting are discussing what the Doctors were discussing for allo patients around 13 years ago. As Dr. Rajkumar noted, LONG TERM followup (IMO 10 years minimum ) in randomized trials is needed before you can draw definitive conclusions if a therapy or response level truly correlates with a superior outcome in the majority of patients. A lot of the importance of MRD testing IMO relates to the patients thoughts. I would not be comfortable treating to anything less than a molecular CR (PCR negative). Other patients are fine with low levels of disease. Like just about everything else relating to myeloma therapy there is no right or wrong answer.
Mark
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Mark
Re: Minimal residual disease (MRD) testing - experiences?
Thanks for your responses Alex and Mark.
You are right it is not new at all as many patients treated for other blood related cancers use MRD
When I was diagnosed I spent burly 8 months on various novel drugs with limited response, I even did the VDT PACE without much success so went to auto transplant. First one I achieved a VGPR so had another one 3 months later which got me into remission. That was a year ago. Since the transplants I have been on Kyprolis for maintenance every other month and whilst the side effects are minimal and my quality of life is pretty good I have to question should I continue and for how long.
I know there is no way of knowing but my logical thinking tells me that if I have achieved MRD negative then the chance of it returning sometime soon would be much less the. If I was MRD positive.
Therefore I would want to give my poor body and veins a break from all the poison !!
I am seeing my Onc next week so will check with her.
Other than the expense I cannot see why the testing has not been are available before. Do the doctors want to keep us on chemo drugs for longer than necessary?
Just my thoughts.
You are right it is not new at all as many patients treated for other blood related cancers use MRD
When I was diagnosed I spent burly 8 months on various novel drugs with limited response, I even did the VDT PACE without much success so went to auto transplant. First one I achieved a VGPR so had another one 3 months later which got me into remission. That was a year ago. Since the transplants I have been on Kyprolis for maintenance every other month and whilst the side effects are minimal and my quality of life is pretty good I have to question should I continue and for how long.
I know there is no way of knowing but my logical thinking tells me that if I have achieved MRD negative then the chance of it returning sometime soon would be much less the. If I was MRD positive.
Therefore I would want to give my poor body and veins a break from all the poison !!
I am seeing my Onc next week so will check with her.
Other than the expense I cannot see why the testing has not been are available before. Do the doctors want to keep us on chemo drugs for longer than necessary?
Just my thoughts.
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meeshymeesh - Name: Michelle
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: 2009
- Age at diagnosis: 40
Re: Minimal residual disease (MRD) testing - experiences?
Hello,
I don't think that it's because the doctors wanted to keep you on the meds for longer than necessary. My mom's maintenance routine was stopped long before MRD by flow cytometry was evaluated with her bone marrow cells.
I think it's really important to note that there isn't a whole lot that can be concluded with MRD flow results, in the context of myeloma. Perhaps we can say much more years down the road. For now, the more meaningful, but prohibitively expensive and sometimes not possible assay is to look at CR at the molecular level, as Mark said.
I don't think that it's because the doctors wanted to keep you on the meds for longer than necessary. My mom's maintenance routine was stopped long before MRD by flow cytometry was evaluated with her bone marrow cells.
I think it's really important to note that there isn't a whole lot that can be concluded with MRD flow results, in the context of myeloma. Perhaps we can say much more years down the road. For now, the more meaningful, but prohibitively expensive and sometimes not possible assay is to look at CR at the molecular level, as Mark said.
-
dnalex - Name: Alex N.
- Who do you know with myeloma?: mother
- When were you/they diagnosed?: 2007
- Age at diagnosis: 56
Re: Minimal residual disease (MRD) testing - experiences?
I too am hoping for usefulness of MRD to allow patients to discontinue maintenance therapy with testing to perhaps signal the need to restart the therapy before the disease can progress.
I achieved near complete response after tandem autologous PBSC transplants. I then was placed on Revlimid and achieved "Complete Remission" with traditional flow cytometry. Now that they have the MRD testing I have been found to have Low MRD. I have been on Revlimid for 5 years now. I would love to be able to stop the Revlimid and monitor MRD.
Is anyone doing research on the effectiveness of restarting maintenance therapies with the detection of increasing MRD?
I achieved near complete response after tandem autologous PBSC transplants. I then was placed on Revlimid and achieved "Complete Remission" with traditional flow cytometry. Now that they have the MRD testing I have been found to have Low MRD. I have been on Revlimid for 5 years now. I would love to be able to stop the Revlimid and monitor MRD.
Is anyone doing research on the effectiveness of restarting maintenance therapies with the detection of increasing MRD?
-
WendyB - Name: Wendy B
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: October 2006
- Age at diagnosis: 41
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