Hi Suzierose and Mark...those are interesting findings, and highly sophisticated research too. My question now is, if one is found to still have a low level of tumour cells, even after a CR, as determined by blood tests, and a BMB, but as seen in the more sensitive MR testing, then what would be the outcome for treatment? Probably the patient would be put back on treatment, or have the treatments changed. Is there an advantage to knowing the results of an MR sooner than waiting for the monoclonal proteins to show up in the blood?
Also, and this is puzzling to me and you might have studied it, isn't the condition of SMM associated also with having monoclonal proteins in the blood? I was never so relieved to find that those M proteins were not detectable any more, since I associate them with the bone damage, and of course they cause problems for the kidneys and heart too! So why is it acceptable to have a level of less than 10% in the patients blood? Not a doctor of course, but just call me curious!
Forums
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Precision Medicine will be in Action @ ASCO 2012
Suzierose, Nancy S.,
I have put this link up and attempted to copy and paste this chart on a few occasions in the past. It is a chart that shows the actual burden based on different responses. As you can see, a patient with a CR with negative immunofixation could have MORE tumor cells than a patient in PR. A stringent Complete Response is not necessarily a deep response. I hope this chart copy and pastes properly:
Response Criteria Tumor gene
copy number
Diagnosis 25,000 - 500,000
PR 5,000 – 100,000
VGPR 1,500 – 20,000
Immunofixation-negative CR 1,000 – 10,000
Immunophenotypic CR* 10 – 100
Molecular CR^ 5 – 20
*Paiva et al Blood 2009;114;4369-72; ^Ladetto et al. J Clin Oncol 2010;28:2077-84
http://myeloma.org/pdfs/Best-of-ASH-2011_01-25-12.pdf
You both might find this kind of funny. I read other patients get very excited when their Doctors tell them they are in CR. I had to do an Auto before my Insurance Co. would pay for the Allo, so neither my Doctor nor I wanted to do the Auto because we thought the Induction would get me to CR. Prior to Auto I was in VGPR. After the Auto I had the definition of CR but not stringent CR. When I got news of my CR I heard things like we have to use higher conditioning (Chemo) for the Allo because you have so much cancer left, the Auto did not work that well, etc. I think I am the only patient that viewed getting to CR as not so great news!
Mark
I have put this link up and attempted to copy and paste this chart on a few occasions in the past. It is a chart that shows the actual burden based on different responses. As you can see, a patient with a CR with negative immunofixation could have MORE tumor cells than a patient in PR. A stringent Complete Response is not necessarily a deep response. I hope this chart copy and pastes properly:
Response Criteria Tumor gene
copy number
Diagnosis 25,000 - 500,000
PR 5,000 – 100,000
VGPR 1,500 – 20,000
Immunofixation-negative CR 1,000 – 10,000
Immunophenotypic CR* 10 – 100
Molecular CR^ 5 – 20
*Paiva et al Blood 2009;114;4369-72; ^Ladetto et al. J Clin Oncol 2010;28:2077-84
http://myeloma.org/pdfs/Best-of-ASH-2011_01-25-12.pdf
You both might find this kind of funny. I read other patients get very excited when their Doctors tell them they are in CR. I had to do an Auto before my Insurance Co. would pay for the Allo, so neither my Doctor nor I wanted to do the Auto because we thought the Induction would get me to CR. Prior to Auto I was in VGPR. After the Auto I had the definition of CR but not stringent CR. When I got news of my CR I heard things like we have to use higher conditioning (Chemo) for the Allo because you have so much cancer left, the Auto did not work that well, etc. I think I am the only patient that viewed getting to CR as not so great news!
Mark
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Mark
Re: Precision Medicine will be in Action @ ASCO 2012
Thanks Mark....I have to admit that some of this science is going over my head...but I gather from what you are saying is that the MR test can detect tumour cells even for a patient in a CR, and they might be in greater quantities than for another patient with a PR (as shown by immunofixation). That's too bad really, since a CR is a cause for a sigh of relief as far as myeloma is concerned, usually. I can see how the MR test might be useful in situations such as yours where you were dealing with an insurance co. and trying to get clearance for an 'allo' transplant. So thanks for all the info and trying to explain this area of myeloma research! And hope you stay well too!
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Precision Medicine will be in Action @ ASCO 2012
Terry, I'll be going to NIH in July. They may ask me to participate in the cafilzomib trial for SMM. Depends on whether they'll consider me a high risk SMM patient.
Were you being treated previously? Are they combining it with other drugs?
I've got so many questions.
Were you being treated previously? Are they combining it with other drugs?
I've got so many questions.
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Stan W. - Name: Stan
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: SMM-April 2012
- Age at diagnosis: 58
Re: Precision Medicine will be in Action @ ASCO 2012
HI Nancy!
you write:
"My question now is, if one is found to still have a low level of tumour cells, even after a CR, as determined by blood tests, and a BMB, but as seen in the more sensitive MR testing, then what would be the outcome for treatment? Probably the patient would be put back on treatment, or have the treatments changed. Is there an advantage to knowing the results of an MR sooner than waiting for the monoclonal proteins to show up in the blood?"
The results of an BM, are that you are not waiting for it to show up in blood. The blood detects secretion of multiple myeloma cells, but does not tell you how many are there..you could have a few cells producing a lot, or many cells secreting a little. And since the BM is highly variable you want more definite tests as it does not indicate # of cells as it could hit a 'hot' spot or not 'so hot' spot. Hematologic tests are surrogates, they do not tell you how many cells are left, only the amount M protein (M spike) being secreting by a few/many cells. Which accounts for PR's having better PFS than some CR's.
So, in terms of therapy, you would want to drive that number down with additional therapy if there are cells left if necessary vs. ending the number of cycles prescribed. Does that make sense?
Overall, what one is looking for is no MRD (minimal residual disease) each test has a different level of sensisitivity, so you want to have no MRD on the lowest sensitivity detectable disease.
"That's too bad really, since a CR is a cause for a sigh of relief as far as myeloma is concerned"
The outcome of therapy, as measured in clinical trials is a CR, the question is what is the depth of response(DOR)? Since all CR's are not equal based on level of sensitivity of test used. If the test has a higher level of sensitivity, the CR, could show that you have no MRD..but if you then have a test with an even greater level of sensitivity if could show there are still cells( IF vs IR). So the objective is to have the test with the highest level of sensitivity have a negative outcome ( no multiple myeloma cells) as that demonstrates greatest DOR. The test with highest sensitivity is PCR for MR.
That is to say that all CR's are not equal based on the level of sensitivity that the test can detect.
So, in the example Mark gave, the test which will show the greatest level of sensitivity (detect lowest number of cells) would be the PCR. So, if you reached CR with IF, you could still have have I0K multiple myeloma cells, whereas with IR it would be less than 100 and as low as 10...but if you have a MR...that number of cells would be lower than 5 cells and a maximum of 20 cells. Best DOR. Which would be awesome!!
The big difference here is that the tests for MR are not measuring how much M protein the cells are secreting but is quantative for the NUMBER of cells that are still there. The goal is least number of cells...equal sustainable CR.
Hope that makes sense...if not ...ASK away!!
you write:
"My question now is, if one is found to still have a low level of tumour cells, even after a CR, as determined by blood tests, and a BMB, but as seen in the more sensitive MR testing, then what would be the outcome for treatment? Probably the patient would be put back on treatment, or have the treatments changed. Is there an advantage to knowing the results of an MR sooner than waiting for the monoclonal proteins to show up in the blood?"
The results of an BM, are that you are not waiting for it to show up in blood. The blood detects secretion of multiple myeloma cells, but does not tell you how many are there..you could have a few cells producing a lot, or many cells secreting a little. And since the BM is highly variable you want more definite tests as it does not indicate # of cells as it could hit a 'hot' spot or not 'so hot' spot. Hematologic tests are surrogates, they do not tell you how many cells are left, only the amount M protein (M spike) being secreting by a few/many cells. Which accounts for PR's having better PFS than some CR's.
So, in terms of therapy, you would want to drive that number down with additional therapy if there are cells left if necessary vs. ending the number of cycles prescribed. Does that make sense?
Overall, what one is looking for is no MRD (minimal residual disease) each test has a different level of sensisitivity, so you want to have no MRD on the lowest sensitivity detectable disease.
"That's too bad really, since a CR is a cause for a sigh of relief as far as myeloma is concerned"
The outcome of therapy, as measured in clinical trials is a CR, the question is what is the depth of response(DOR)? Since all CR's are not equal based on level of sensitivity of test used. If the test has a higher level of sensitivity, the CR, could show that you have no MRD..but if you then have a test with an even greater level of sensitivity if could show there are still cells( IF vs IR). So the objective is to have the test with the highest level of sensitivity have a negative outcome ( no multiple myeloma cells) as that demonstrates greatest DOR. The test with highest sensitivity is PCR for MR.
That is to say that all CR's are not equal based on the level of sensitivity that the test can detect.
So, in the example Mark gave, the test which will show the greatest level of sensitivity (detect lowest number of cells) would be the PCR. So, if you reached CR with IF, you could still have have I0K multiple myeloma cells, whereas with IR it would be less than 100 and as low as 10...but if you have a MR...that number of cells would be lower than 5 cells and a maximum of 20 cells. Best DOR. Which would be awesome!!
The big difference here is that the tests for MR are not measuring how much M protein the cells are secreting but is quantative for the NUMBER of cells that are still there. The goal is least number of cells...equal sustainable CR.
Hope that makes sense...if not ...ASK away!!
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Precision Medicine will be in Action @ ASCO 2012
Hi Stan, I was dx. with myeloma last summer. I was considered to be smoldering and last September, I entered the NIH study of the progression of myeloma. Unfortunately, I progressed to active myeloma in April due to a pulmonary embolism and a plummeting hemoglobin-----remember the CRAB criteria....I hit the A in a big way. Until Dr. Landgren admitted me to the carfilzomib trial, I had never been treated and was simply monitored. I was considered high risk for progression to active myeloma due to several factors----immune paresis and a high plasma cell infiltration (70% plus). If you are high risk for progression due to these and other factors, you probably qualify. If you need any more info., please contact me. The care I receive at the NIH is outstanding and they leave no stone unturned in terms of care, monitoring, testing, etc. I lucked out by being offered a slot---no doubt in my mind. Terry L.
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terryl1 - Name: Terry
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August 10, 2011
- Age at diagnosis: 49
Re: Precision Medicine will be in Action @ ASCO 2012
Hi Suzierose, Thanks for your reply. I can certainly appreciate that the more sensitive is the test for plasma cells, the more 'accurate' the treatment can be. Good if this sort of testing were to eventually be widely available, at the time of the initial 'CR', as noted in a BMB....then treatments could be adjusted accordingly. I appreciate reading your scientific postings....lots of thought goes into them. in the meanwhile, the Immunofixation tests and the BMB's certainly give one an indication of the overall 'tumour burden'. A 'cure' thus remains elusive...one can just hope for a good long remission, with or without a CR. Hope that makes sense...multiple myeloma science is nothing if not confusing at times!
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Precision Medicine will be in Action @ ASCO 2012
Hi Nancy,
I agree with you.
Hope springs eternal!! I am with you on that!!
We are making advances everyday in multiple myeloma and I have lots of optimism about the choices we have.
I am hopeful that all patients see the day where the testing criteria in trials reflects the tumor load and not just 'responses' to surrogate markers that reflect M protein.
I can't tell you how fervently I pray for effective trial outcomes that truly demonstrate a difference and give all of us with this disease a manageable disease at least and a cure at best!!
It may be elusive, but the dawn is on the horizon, and Precision Medicine will pave the way!!
Let's all cheer for the scientists who dedicate themselves to delineating that difference and work hard to demonstrate there is a path for the cure!!
I agree with you.
Hope springs eternal!! I am with you on that!!
We are making advances everyday in multiple myeloma and I have lots of optimism about the choices we have.
I am hopeful that all patients see the day where the testing criteria in trials reflects the tumor load and not just 'responses' to surrogate markers that reflect M protein.
I can't tell you how fervently I pray for effective trial outcomes that truly demonstrate a difference and give all of us with this disease a manageable disease at least and a cure at best!!
It may be elusive, but the dawn is on the horizon, and Precision Medicine will pave the way!!
Let's all cheer for the scientists who dedicate themselves to delineating that difference and work hard to demonstrate there is a path for the cure!!
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
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