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What's a transplant "success" if in CR pre-transplant?
If one has achieved complete remission, or even stringent complete remission, and then proceeds to a stem cell transplant, how will the doctors know whether the transplant has been successful or not?
Re: What's a transplant "success" if in CR pre-transplant?
Excellent question. There is no immediate way to know if transplant is a success if you are in a CR pre-transplant. The only way to know is by the duration of remission post-transplant.
While not routinely done, there are tests now available beyond the serum and urine immunofixation tests that may be able to tell if the "response" improves with transplant. The test that seems most reliable is called deep sequencing to test for "minimal residual disease." This requires a bone marrow sample to run. The first test can be done on a pre-transplant bone marrow sample, but the second test would require another bone marrow biopsy about 3 months post transplant.
While not routinely done, there are tests now available beyond the serum and urine immunofixation tests that may be able to tell if the "response" improves with transplant. The test that seems most reliable is called deep sequencing to test for "minimal residual disease." This requires a bone marrow sample to run. The first test can be done on a pre-transplant bone marrow sample, but the second test would require another bone marrow biopsy about 3 months post transplant.
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Dr. Jason Valent - Name: Jason Valent, M.D.
Beacon Medical Advisor
Re: What's a transplant "success" if in CR pre-transplant?
Thank you so much. This is the kind of response I was hoping for.
Re: What's a transplant "success" if in CR pre-transplant?
Even with deep sequencing, is there a possibility that the bone marrow biopsy may be from a region where there is no disease present, but there could be regions elsewhere that have disease – maybe even a lot?
Would this result in a 'no detectable disease' result when there could still be disease present?
Would this result in a 'no detectable disease' result when there could still be disease present?
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Eric Hofacket - Name: Eric H
- When were you/they diagnosed?: 01 April 2011
- Age at diagnosis: 44
Re: What's a transplant "success" if in CR pre-transplant?
If you don't do the MRD test, how do you know that the duration of remission is really due to the transplant?
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coachhoke - Name: coachhoke
- When were you/they diagnosed?: Apri 2012
- Age at diagnosis: 71
Re: What's a transplant "success" if in CR pre-transplant?
Hi mrozdav,
With the overall survival of myeloma patients rising, it is difficult to know what the contribution of the different drugs is for each individual patient. My perception of the benefit of high-dose alkylators (auto) is that some patients can have long-term, drug-free remissions and enjoy excellent quality of life if they do them as part of upfront therapy.
You may have discussed maintenance therapy with your doctor. If he/she is planning on keeping you on maintenance no matter what your response is if you do the transplant, you could ask them what they think the benefit of the transplant would be in your individual case.
There was a study at ASH 2014 that showed the patients most likely to benefit from upfront auto are those that achieve VGPR [very good partial response] or better from induction. No mention if CR was even more favorable in this study. This study is interesting as it breaks patients down by age so this study could be helpful for older patients considering auto.
Another study at ASH 2014 showed a similar result in that patients that responded well to induction benefited most from early auto. CC+R is chemotherapy plus Revlimid.
In my opinion, the success of therapy should really factor in quality of life. One of the main reasons I consider my therapy a success at this point is that the drug-free remission period has provided me with an excellent quality of life.
One follow-up question I would have is whether, if a patient is MRD negative after induction, doctors typically have them use maintenance.
Mark
With the overall survival of myeloma patients rising, it is difficult to know what the contribution of the different drugs is for each individual patient. My perception of the benefit of high-dose alkylators (auto) is that some patients can have long-term, drug-free remissions and enjoy excellent quality of life if they do them as part of upfront therapy.
You may have discussed maintenance therapy with your doctor. If he/she is planning on keeping you on maintenance no matter what your response is if you do the transplant, you could ask them what they think the benefit of the transplant would be in your individual case.
There was a study at ASH 2014 that showed the patients most likely to benefit from upfront auto are those that achieve VGPR [very good partial response] or better from induction. No mention if CR was even more favorable in this study. This study is interesting as it breaks patients down by age so this study could be helpful for older patients considering auto.
In multivariate analysis, variables predictive of OS included age, disease stage, and year of transplant; whereas for DFS, predictive variables also included disease status at transplant and planned tandem ASCT (see table). This analysis builds on a growing body of evidence suggesting improved outcomes in patients with multiple myeloma. Patients regardless of age appear to benefit from ASCT, with median survival now exceeding 5 years in all age groups. Patients less than 55 years of age and particularly those achieving at least a VGPR prior to ASCT seem to represent a patient population with an extremely favorable prognosis post-transplant.
J LaPorte et al, "Age Related Outcomes for Multiple Myeloma Patients Following Autologous Transplantation, ASH 2014 abstract 3968 (link to abstract)
Another study at ASH 2014 showed a similar result in that patients that responded well to induction benefited most from early auto. CC+R is chemotherapy plus Revlimid.
In NDMM patients, Mel200-ASCT significantly improved PFS and OS in comparison with CC+R. The most significant OS advantage was observed in patients with baseline Karnofsky PS 80-100%, ISS Stage I, with absence of del17, t(4;14) or t(14;16) and in patients achieving ≥VGPR after induction. These data suggest intensifying treatment in good-prognosis patients and in patients with a chemo-sensitive disease. More effective novel agents are needed for patients with a more aggressive disease.
F Gay et al, "Impact of Autologous Transplantation Vs. Chemotherapy Plus Lenalidomide in Newly Diagnosed Myeloma According to Patient Prognosis: Results of a Pooled Analysis of 2 Phase III Trials," ASH 2014 abstract 79 (link to abstract)
In my opinion, the success of therapy should really factor in quality of life. One of the main reasons I consider my therapy a success at this point is that the drug-free remission period has provided me with an excellent quality of life.
One follow-up question I would have is whether, if a patient is MRD negative after induction, doctors typically have them use maintenance.
Mark
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Mark11
Re: What's a transplant "success" if in CR pre-transplant?
Eric Hofacket asked:
Hi Eric,
The answer to your question is "Yes", for at least two reasons.
First, as you indicate, the tested bone marrow sample may show no sign of residual disease, but a sample elsewhere might show signs of the disease.
One common sign that this happens is that sometimes you will see studies reporting that patients who have not achieved a complete response (i.e., still have an M-spike) nevertheless test MRD negative.
Second, bear in mind that MRD testing is not perfect. Even the most sensitive MRD tests available do not test each and every cell in the bone marrow. So, even if you could test all of a patient's bone marrow, the tests could still miss myeloma cells that are present.
And, of course, there's the added complication that myeloma cells could be elsewhere in the body, not just in the bone marrow.
There was a lot of discussion of these issues related to MRD testing in the comments on an article The Beacon published last July,
"Treatment Regimen Featuring Revlimid-Velcade-Dexamethasone Therapy And Stem Cell Transplantation Yields Deep Responses In Newly Diagnosed Multiple Myeloma," The Myeloma Beacon, Jul 16, 2014.
You'll find the relevant comments if you scan all of them, looking for mentions of "MRD" or "minimal residual disease". (Mark11, who posted above in this thread, will remember the discussion in the comments to the article, since he participated in it ... as did another reader also named Mark.)
Thanks for the question, Eric.
Even with deep sequencing, is there a possibility that the bone marrow biopsy may be from a region where there is no disease present, but there could be regions elsewhere that have disease – maybe even a lot?
Would this result in a 'no detectable disease' result when there could still be disease present?
Hi Eric,
The answer to your question is "Yes", for at least two reasons.
First, as you indicate, the tested bone marrow sample may show no sign of residual disease, but a sample elsewhere might show signs of the disease.
One common sign that this happens is that sometimes you will see studies reporting that patients who have not achieved a complete response (i.e., still have an M-spike) nevertheless test MRD negative.
Second, bear in mind that MRD testing is not perfect. Even the most sensitive MRD tests available do not test each and every cell in the bone marrow. So, even if you could test all of a patient's bone marrow, the tests could still miss myeloma cells that are present.
And, of course, there's the added complication that myeloma cells could be elsewhere in the body, not just in the bone marrow.
There was a lot of discussion of these issues related to MRD testing in the comments on an article The Beacon published last July,
"Treatment Regimen Featuring Revlimid-Velcade-Dexamethasone Therapy And Stem Cell Transplantation Yields Deep Responses In Newly Diagnosed Multiple Myeloma," The Myeloma Beacon, Jul 16, 2014.
You'll find the relevant comments if you scan all of them, looking for mentions of "MRD" or "minimal residual disease". (Mark11, who posted above in this thread, will remember the discussion in the comments to the article, since he participated in it ... as did another reader also named Mark.)
Thanks for the question, Eric.
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Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: What's a transplant "success" if in CR pre-transplant?
Quite a bit to go through. This is an excellent high-level discussion.
Minimal residual disease (MRD) testing for myeloma is relatively new. Since we are not curing people with conventional chemotherapy or autologous transplant, one can argue that there really is no point to even doing it until more data is available on how to best use this test. What ultimately determines success of any treatment is that patients live a long time. We know that patients treated with conventional therapy are not cured even though they are MRD negative.
The MRD test has limitations to detecting about 1 in 100,000 myeloma cells at the second testing point that had a specific genetic signature at the time the baseline test was run. And, yes, the marrow can be "patchy" with respect to where the myeloma cells actually are located, and bone marrow biopsies are not able to specifically target where the myeloma cells are.
To the question about MRD negative patients after transplant and the need for maintenance ... This question will probably be answered in the future, but there is not enough science currently to answer this question with absolute certainty. Our current practice is to offer maintenance therapy to all transplant patients after a detailed discussion about specific risks and potential benefit.
Quality of life is very important to me as well. This is often NOT studied in maintenance chemotherapy trials. Practically speaking, if a patient is in CR and not tolerating maintenance therapy, I am much more likely to discontinue it than if a patient is not in CR. The abstract mentioned from ASH is important because it provides science to support this type of decision.
Minimal residual disease (MRD) testing for myeloma is relatively new. Since we are not curing people with conventional chemotherapy or autologous transplant, one can argue that there really is no point to even doing it until more data is available on how to best use this test. What ultimately determines success of any treatment is that patients live a long time. We know that patients treated with conventional therapy are not cured even though they are MRD negative.
The MRD test has limitations to detecting about 1 in 100,000 myeloma cells at the second testing point that had a specific genetic signature at the time the baseline test was run. And, yes, the marrow can be "patchy" with respect to where the myeloma cells actually are located, and bone marrow biopsies are not able to specifically target where the myeloma cells are.
To the question about MRD negative patients after transplant and the need for maintenance ... This question will probably be answered in the future, but there is not enough science currently to answer this question with absolute certainty. Our current practice is to offer maintenance therapy to all transplant patients after a detailed discussion about specific risks and potential benefit.
Quality of life is very important to me as well. This is often NOT studied in maintenance chemotherapy trials. Practically speaking, if a patient is in CR and not tolerating maintenance therapy, I am much more likely to discontinue it than if a patient is not in CR. The abstract mentioned from ASH is important because it provides science to support this type of decision.
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Dr. Jason Valent - Name: Jason Valent, M.D.
Beacon Medical Advisor
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