I was reading the latest Mayo mSmart treatment guidelines for a person newly diagnosed with multiple myeloma. It indicates that a person with high risk multiple myeloma would have four cycles of VRd and proceed with the autologous stem cell transplant, especially if not in CR.
For most benefit from the stem cell transplant, shouldn't a patient continue induction therapy to try and gain CR?
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Re: Only 4 cycles VRd pre-ASCT for high-risk myeloma?
I am guessing that is just a general guideline on standard treatment. Each myeloma patient is unique with different factors to be considered. I am high risk and I had 4 cycles of CyBorD (cyclophosphamide, Velcade, and dexamethasone). This brought me to a 0.1 g/dL (1 g/L) M-spike. My transplant doctor then gave me a high dose of Cytoxan in an attempt to get my M spike even lower. Yes, it was preferred to get it as low as possible.
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kjpoppit - Name: Kim Nelson
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Sept. 19th, 2013
- Age at diagnosis: 47
Re: Only 4 cycles VRd pre-ASCT for high-risk myeloma?
H Spirit and kjpoppit,
You might also be interested in this recent Beacon research review article summarizing a study where the researchers found no difference between groups of patients receiving "standard" induction therapy prior to SCT vs. those receiving additional treatment aimed to achieve a deeper response prior to the SCT. (https://myelomabeacon.org/news/2015/03/23/pre-transplant-depth-of-response-multiple-myeloma/)
I don't think the study looked at high-risk vs. standard risk patients, though.
Mike
You might also be interested in this recent Beacon research review article summarizing a study where the researchers found no difference between groups of patients receiving "standard" induction therapy prior to SCT vs. those receiving additional treatment aimed to achieve a deeper response prior to the SCT. (https://myelomabeacon.org/news/2015/03/23/pre-transplant-depth-of-response-multiple-myeloma/)
I don't think the study looked at high-risk vs. standard risk patients, though.
Mike
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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: Only 4 cycles VRd pre-ASCT for high-risk myeloma?
Hello Spirit:
You have asked a question that, although seemingly simple, I have heard extensive debates from the top myeloma docs. So please do your research, but I will try and give you a simplistic answer based on my recent readings.
If your response is that you are clearly "responding" (based on blood test #'s), continue beyond 4 cycles, up to "plateau", but the continuation of rounds by most of the recent literature will top out at about 8.
My read of the tendency for 4 rounds is that it was based on older meds with higher side effects (toxicities), and that despite the issues you hear with RVD (and other novel agents), they have a lot fewer toxicities than older drugs. Stopping at 4 is not necessarily "Gospel".
Also, if you are a patient at the Mayo clinic (we are not) MSmart, I am sure will tweak the overall guidelines based on individual circumstances. Another consideration, of course, is insurance approval.
In fact, some of the rounds (up to 8) can occur after the ASCT. The rounds after the ASCT are considered post-ASCT consolidation. The total of rounds, I have heard from the docs, adding up pre- and post-ASCT could go to 8. If you get to a good result, then you can stop before 8. The original 4 might be good enough, and you may not need more than the traditional 4.
One last point, reaching CR is a good thing, however, the newer question is: Did you reach MRD- [minimal residual disease negative]?? If you plateaued and could not reach MRD-, then you may just be whacking yourself with additional unnecessary treatment; HOWEVER, if you have not yet reached MRD-, AND you have not yet plateaued, you may consider additional treatments.
I know it's confusing, but I hope this helps a little.
Regards,
You have asked a question that, although seemingly simple, I have heard extensive debates from the top myeloma docs. So please do your research, but I will try and give you a simplistic answer based on my recent readings.
If your response is that you are clearly "responding" (based on blood test #'s), continue beyond 4 cycles, up to "plateau", but the continuation of rounds by most of the recent literature will top out at about 8.
My read of the tendency for 4 rounds is that it was based on older meds with higher side effects (toxicities), and that despite the issues you hear with RVD (and other novel agents), they have a lot fewer toxicities than older drugs. Stopping at 4 is not necessarily "Gospel".
Also, if you are a patient at the Mayo clinic (we are not) MSmart, I am sure will tweak the overall guidelines based on individual circumstances. Another consideration, of course, is insurance approval.
In fact, some of the rounds (up to 8) can occur after the ASCT. The rounds after the ASCT are considered post-ASCT consolidation. The total of rounds, I have heard from the docs, adding up pre- and post-ASCT could go to 8. If you get to a good result, then you can stop before 8. The original 4 might be good enough, and you may not need more than the traditional 4.
One last point, reaching CR is a good thing, however, the newer question is: Did you reach MRD- [minimal residual disease negative]?? If you plateaued and could not reach MRD-, then you may just be whacking yourself with additional unnecessary treatment; HOWEVER, if you have not yet reached MRD-, AND you have not yet plateaued, you may consider additional treatments.
I know it's confusing, but I hope this helps a little.
Regards,
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JPC - Name: JPC
Re: Only 4 cycles VRd pre-ASCT for high-risk myeloma?
Thank you for your comments. They are very much appreciated.
Re: Only 4 cycles VRd pre-ASCT for high-risk myeloma?
JPC,
Do you know if a bone marrow biopsy is required to determine if you have minimal residual disease (MRD)?
RT
Do you know if a bone marrow biopsy is required to determine if you have minimal residual disease (MRD)?
RT
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RadiantTiger - Name: Radiant Tiger
- Who do you know with myeloma?: Myself, my deceased uncle
- When were you/they diagnosed?: Feb 2015
- Age at diagnosis: 54
Re: Only 4 cycles VRd pre-ASCT for high-risk myeloma?
Yes, RadiantTiger, you need a bone marrow biopsy for minimal residual disease testing.
There are MRD tests being researched that would rely on blood samples rather than marrow biopsy samples. But they are still in the very early stages of development.
There are MRD tests being researched that would rely on blood samples rather than marrow biopsy samples. But they are still in the very early stages of development.
Re: Only 4 cycles VRd pre-ASCT for high-risk myeloma?
Good morning RadiantT:
Adding a little bit to Ian's quite succinct and direct reply, the testing for minimal residual disease in multiple myeloma is done on the bone marrow aspirate (the blood-like fluid inside the bone, not the marrow). So yes, it needs to be done during a BMB. Evidence of myeloma cells has been found floating around in the aspirate when there is evidence of zero myeloma in the marrow. That is why its a more sensitive test. You could be CR or sCR and still be MRD positive (they find cells floating in the aspirate). Recent research seems to indicate that MRD negative status is noticeably better over the long run than either CR or sCR; however, it is recent and incomplete evidence based on the relative newness of the test. If you are not CR, it makes no sense to test for MRD, generally.
Keep in mind, however, that depending on your particular case and treatment needs / plan, that it very well could be the case that it would not have to be an "extra" BMB. The test would be done on the sample taken at a time when you would be getting the BMB anyway.
MRD testing in multiple myeloma and other cancers is still relatively new. I have read that there is still a "standards" problem, and leading doctors are working on developing better standards. For instance, a test on a sample in one center with a less sensitive version of the test will get you MRD -, where another center has a more sensitive test, and would yield an MRD + result, for the same sample. Here is a link that discusses that issue. Between the link and its references, there is a lot of material on the subject.
"Minimal Residual Disease: What Are the Minimum Requirements?", Journal of Clinical Oncology, February 2014 (link to full text of article)
As with many other aspects of multiple myeloma, this also has its complexities, so please do your research, but long story short, if you reach CR, you want to get the test to find out if you reached MRD negativity, and the answer to that question may inform you and your doctor in certain treatment decisions. Regards, Hope this helps.
Adding a little bit to Ian's quite succinct and direct reply, the testing for minimal residual disease in multiple myeloma is done on the bone marrow aspirate (the blood-like fluid inside the bone, not the marrow). So yes, it needs to be done during a BMB. Evidence of myeloma cells has been found floating around in the aspirate when there is evidence of zero myeloma in the marrow. That is why its a more sensitive test. You could be CR or sCR and still be MRD positive (they find cells floating in the aspirate). Recent research seems to indicate that MRD negative status is noticeably better over the long run than either CR or sCR; however, it is recent and incomplete evidence based on the relative newness of the test. If you are not CR, it makes no sense to test for MRD, generally.
Keep in mind, however, that depending on your particular case and treatment needs / plan, that it very well could be the case that it would not have to be an "extra" BMB. The test would be done on the sample taken at a time when you would be getting the BMB anyway.
MRD testing in multiple myeloma and other cancers is still relatively new. I have read that there is still a "standards" problem, and leading doctors are working on developing better standards. For instance, a test on a sample in one center with a less sensitive version of the test will get you MRD -, where another center has a more sensitive test, and would yield an MRD + result, for the same sample. Here is a link that discusses that issue. Between the link and its references, there is a lot of material on the subject.
"Minimal Residual Disease: What Are the Minimum Requirements?", Journal of Clinical Oncology, February 2014 (link to full text of article)
As with many other aspects of multiple myeloma, this also has its complexities, so please do your research, but long story short, if you reach CR, you want to get the test to find out if you reached MRD negativity, and the answer to that question may inform you and your doctor in certain treatment decisions. Regards, Hope this helps.
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JPC - Name: JPC
Re: Only 4 cycles VRd pre-ASCT for high-risk myeloma?
Very helpful explanations in this thread. I really appreciate the posters taking the time to write them.
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kemscm - Name: Kate
- Who do you know with myeloma?: Me (possibly)
- When were you/they diagnosed?: In process
- Age at diagnosis: 63
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