Nanct S - I have to have a Bone Marrow biopsy every 6 months. They do a PCR test to determine my level of remission. I am like you since I had compression fractures (3) at my diagnosis. As great as it is to hear I am in remission, seeing the results of the PET scan remind me just how much damage the myeloma did to my bones. I hate doing the bone marrow biopsies, but I do get a reward for it. If my MR holds I do not have to treat, so that helps makes up for the frequent BMBs!
Suzierose - One of the things I remember about my stay in the BMT for my Allo is that it was during the NBA Finals last year. It is not all that easy to sleep there since you are being so closely monitored. My last check at night was around 11 PM and my first check in the AM was 5 AM. If you remember, Game 2 was the game the Heat had a 15 point lead in the 4th QTR and the Mavericks came back to win. I went to sleep early in the 4th. I got up at 4 AM and decided to turn on my TV. The game was on Instant Classic on ESPN and I picked it up with 5 minutes to go. I was rooting for the Mavs so I got to see the great comeback and I was watching it with no idea the Mavs won. At least that was one good morning in there!
Terry H, TerryL - Thanks for the well wishes. Please share any good test results with us. My last sweep of the Blogs did not include much good news - especially from "across the pond". It is always uplifting for me to hear of other patients getting good test results.
Forums
Re: Precision Medicine will be in Action @ ASCO 2012
Hi Mark, I guess that was a dumb question anyhow...of course the really detailed type of test for a molecular response would have to be from a BMB. If I have another BMB in the future, I guess I could inquire about it, but haven't had that lovely test since after my stem cell 'transplant', and it came out clear at that time, and the previous one too! so i probably won't have another
one unless or when I relapse, which of course I hope is not for a long time, although of course don't have a crystal ball and the jury is out on that one!
Anyways, hope all continues to go well with you. I know what you mean about bone damage...it is rather frightening but after awhile you just try to work around it and not injure yourself. Everyone in my life rather over protects me now about doing any heavy work, and I do appreciate their concern, although it was a huge adjustment to go from being quite strong to fear of fractures!
Are you still taking bisphosphonates for bone healing? Even though there is a risk of ONJ, I am still on a lower dose of them, since apparently still have bone damage. The good medical folks don't show me any pics of my X-rays, and I don't ask either, just get the report on how it all is going internally. I can tell that my bones are weaker, since strenuous effort results in pain, as well as weather changes from dry to damp (usually the climate where I live is a dry one, albeit cold). But, at my age, lots of my friends have medical problems of some sort or other, so we can commiserate together...yikes! And of course, am monitored regularly with blood tests.
Have a nice weekend....not following sports here since our hockey team, The Flames, flamed out before the playoffs. That happens sometimes!
one unless or when I relapse, which of course I hope is not for a long time, although of course don't have a crystal ball and the jury is out on that one!
Anyways, hope all continues to go well with you. I know what you mean about bone damage...it is rather frightening but after awhile you just try to work around it and not injure yourself. Everyone in my life rather over protects me now about doing any heavy work, and I do appreciate their concern, although it was a huge adjustment to go from being quite strong to fear of fractures!
Are you still taking bisphosphonates for bone healing? Even though there is a risk of ONJ, I am still on a lower dose of them, since apparently still have bone damage. The good medical folks don't show me any pics of my X-rays, and I don't ask either, just get the report on how it all is going internally. I can tell that my bones are weaker, since strenuous effort results in pain, as well as weather changes from dry to damp (usually the climate where I live is a dry one, albeit cold). But, at my age, lots of my friends have medical problems of some sort or other, so we can commiserate together...yikes! And of course, am monitored regularly with blood tests.
Have a nice weekend....not following sports here since our hockey team, The Flames, flamed out before the playoffs. That happens sometimes!
-
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 Mark, You asked about good news and I got some this weekend. It appears that the carfilzomib trial I am in at the NIH is working for me....knock on wood. As you know, I have had a few bumps in the road---pulmonary embolism in April, tanked out hemoglobin, low neutrophils requiring neupogen. However, after seven weeks of treatment with CRd, my blood counts are rising quickly as the plasma cells are being wiped out. In just three weeks, my white blood count more than doubled to 3.5: my neutrophils are now 2.5 ( a few weeks ago they were actually just .33!) and my hemoglobin is now 11.5 (a few weeks ago it was only 8.7). Since I am light chain only, my SPEP's are always normal. We light chain folks don't have traditional M-Spikes. I am awaiting the results of the serum light chain assay which is how my disease is tracked. I realize things could always change, but right now it feels good to be able to exercise again and I feel 100% better than I did a few weeks ago. I feel lucky to have been able to get into the CRd trial. One thing is for sure---carfilzomib works very quickly. Hopefully, it will lead to a durable response. Regards. 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
Nancy S.,
The Hockey season is still going on for me - I am a Devils fan. Tonight could be the bitter end to the season for me. Those Kings are really good - no disgrace if they lose to them.
No such thing as a dumb question. The PCR cannot be set up for all patients. I think it is about 25% of the patients the test cannot be done. You could check if they are doing the flow cytometry test for Immunophenotypic Response. They can be run for everyone. The advantage that test can have for patients like us is that if a patient has an Immunophenotypic response and loses it is an early signal that a relapse is likely. That is important for patients like us because we cannot afford to lose any more bone!
I am on Zometa. I am going to ask next time about long term plans for this. I guess I should get a Bone Density Test and see what that shows. I had one done just before I was diagnosed and it was bad. Hopefully it will be showing some signs of improvement.
Mark
The Hockey season is still going on for me - I am a Devils fan. Tonight could be the bitter end to the season for me. Those Kings are really good - no disgrace if they lose to them.
No such thing as a dumb question. The PCR cannot be set up for all patients. I think it is about 25% of the patients the test cannot be done. You could check if they are doing the flow cytometry test for Immunophenotypic Response. They can be run for everyone. The advantage that test can have for patients like us is that if a patient has an Immunophenotypic response and loses it is an early signal that a relapse is likely. That is important for patients like us because we cannot afford to lose any more bone!
I am on Zometa. I am going to ask next time about long term plans for this. I guess I should get a Bone Density Test and see what that shows. I had one done just before I was diagnosed and it was bad. Hopefully it will be showing some signs of improvement.
Mark
-
Mark
Re: Precision Medicine will be in Action @ ASCO 2012
TerryL,
That is what I like to hear. I have my fingers crossed a Molecular Response is in your near future.
Mark
That is what I like to hear. I have my fingers crossed a Molecular Response is in your near future.
Mark
-
Mark
Re: Precision Medicine will be in Action @ ASCO 2012
Hi Mark!
I am rooting for the Heat!! Who are you rooting for?
you write:
The PCR cannot be set up for all patients. I think it is about 25% of the patients the test cannot be done
Is that so? If so, why...thanks for giving me additional insight. Are we talking a simple matter of probing for the specific cytogenetic abnormalities or what?
I am rooting for the Heat!! Who are you rooting for?
you write:
The PCR cannot be set up for all patients. I think it is about 25% of the patients the test cannot be done
Is that so? If so, why...thanks for giving me additional insight. Are we talking a simple matter of probing for the specific cytogenetic abnormalities or what?
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Precision Medicine will be in Action @ ASCO 2012
Thanks, Mark....as they say, from your mouth to God's ear! 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 Mark...my bones ARE stronger now than at the time of dx, just not as strong as before, but I can't complain really. The worst feeling was when they were literally crumbling. and I could feel it happening!! But now they are stabilized and not being eaten away from within by mutated plasma cells, and I can function more normally again...it took awhile, but it's worth the wait for the improvements to take place. I feel that the aredia I have been taking has made all the different that way, and also one has a natural capacity for healing. After all, people break bones and have them heal up again, since bone is in a constant state of change.
Anyhow, enjoy the hockey. The oddest thing that everyone is commenting on here, is how the former coach of the Flames, Darryl Sutter, left our team and took on a post with the L.A. Kings. Now they are in the Stanley Cup finals while the Flames were still floundering! I guess the change did him a lot of good!
Anyhow, enjoy the hockey. The oddest thing that everyone is commenting on here, is how the former coach of the Flames, Darryl Sutter, left our team and took on a post with the L.A. Kings. Now they are in the Stanley Cup finals while the Flames were still floundering! I guess the change did him a lot of good!
-
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,
I really thought Dirk Nowitzki deserved an NBA title and last year would be his best and last chance. I knew the Heat would have more chances. LeBron probably could not believe what was happening early in that Celtics series. With Bosh out and Wade not playing well he must have felt he was back in Cleveland! I think the Heat will take it.
As far as the PCR testing, the only explanation I ever saw for that was in this paper. You have more of a scientific background than me, so you will probably understand this better than I do.
"The most commonly used PCR method to detect MRD in myeloma is the allele-specific-oligonucleotide (ASO) probe technique. With such an approach, the probe is positioned in a tumor-specific sequence of the patient-specific complementarity-determining region (CDR) of the immunoglobulin heavy chain. Although this technique detects a patient-specific probe in 95–100% of cases with acute and chronic B-lymphocytic leukemias, it will find a patient-specific probe in only 60–80% of myeloma cases. The relatively high failure rate in myeloma is mainly related to the high frequency of somatic mutations in myeloma cells—plasma cells are the most differentiated B cells—generated under antigen selection, as well as to deletions and additions of random nucleotides occurring in the primer target sites during VDJ recombination."
http://www.clinicaladvances.com/article_pdfs/ho-article-200702-tricot.pdf
Mark
I really thought Dirk Nowitzki deserved an NBA title and last year would be his best and last chance. I knew the Heat would have more chances. LeBron probably could not believe what was happening early in that Celtics series. With Bosh out and Wade not playing well he must have felt he was back in Cleveland! I think the Heat will take it.
As far as the PCR testing, the only explanation I ever saw for that was in this paper. You have more of a scientific background than me, so you will probably understand this better than I do.
"The most commonly used PCR method to detect MRD in myeloma is the allele-specific-oligonucleotide (ASO) probe technique. With such an approach, the probe is positioned in a tumor-specific sequence of the patient-specific complementarity-determining region (CDR) of the immunoglobulin heavy chain. Although this technique detects a patient-specific probe in 95–100% of cases with acute and chronic B-lymphocytic leukemias, it will find a patient-specific probe in only 60–80% of myeloma cases. The relatively high failure rate in myeloma is mainly related to the high frequency of somatic mutations in myeloma cells—plasma cells are the most differentiated B cells—generated under antigen selection, as well as to deletions and additions of random nucleotides occurring in the primer target sites during VDJ recombination."
http://www.clinicaladvances.com/article_pdfs/ho-article-200702-tricot.pdf
Mark
-
Mark
Re: Precision Medicine will be in Action @ ASCO 2012
Hi Mark!
I can always rely on you to provide articles with more in-depth information, lol. That's a good thing. As I did learn that F-PCR works for 91% of multiple myeloma patients.
http://www.ncbi.nlm.nih.gov/pubmed/18637804
I soo agree about LeBron missing Bosh. I was happy to see him return it makes a big difference. I like DeWayne Wade and he has an awesome game, but he won a championship with Shaq and has not carried a team on his own. Last year the Heat had to make a transition and now I hope the trio has their timing and roles down better as LeBron is the only one who has ever carried a team on his back and he showed that again in game 7 with Celtics. I think he is ready to carry the Heat all the way to a ring this year!!...but OK Thunder is hungry and young..so this should be a great Finals Series. I hope you are right that the Heat take it all.
The article you linked to on PCR was quite informative for a number of reasons while I found the answer, to how the PCR test is performed in another article,(Gonzalez 2003) which boils down to testing technique and probe failure due to greater mutation rates, as:
.. these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (multiple myeloma) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells....snip..Usually, allele-specific oligonucleotides (ASO) are targeted to the VDJH junction and the TaqMan probe and reverse primer are targeted to JH consensus and intronic regions. In this situation, it is possible that the consensus primers and probe coincide with a somatically mutated JH segment. If this happens, the primer and/or probe will be mismatched and PCR efficiency will be dramatically reduced."
http://www.ncbi.nlm.nih.gov/pubmed/12764368
The mutational difference then for multiple myeloma is highlighted due to PCR techniques not encountering this issue in diseases like leukemia/lymphoma that are characterized primarily by a single mutation that accounts for the disease.
It was the other information that was of far greater value in terms of understanding multiple myeloma pathogenesis.
I have consistently been baffled in terms of PR's and CR's where the former has longer PFS.despite knowing hematologic tests are surrogate tests for multiple myeloma What the article, you cited, made clear is that this is due to measuring paraprotein vs cells.
Ultimately tests such as IF, SPEP, etc are reliant on secretory rates of the multiple myeloma cells which of course varies from patient to patient and is not prognostic for disease aggressiveness. That had been such a big disconnect, when you have a patient classified ISS stage I but yet instill, clinical trials show due to cytogenetics the outcomes are dismal. This of course is due to measuring RESPONSES vs disease cellular load. Whereas, quantitative tests measuring the actual number of cells present gives a far more accurate and sensitive measure of the disease status. Particularly, as it pertains to disease progression rates along with relapses. Thanks to the article you cited, at least, I have an answer to that conundrum finally:
"Although IFE can detect even small amounts of M protein of at least 5 mg/dL, measuring
M proteins is a very poor technique to estimate the remaining tumor load. This technique would be reliable if all myelomas secreted the same amount of immunoglobulin per cell and per day; however, there is a large interpatient and intrapatient variability in immunoglobulin secretion per cell per day. In general, the more mature plasma cells secrete a larger amount of immunoglobulin per day than the immature plasma cells.8 Therefore, it may be more difficult for patients with a mature-appearing myeloma (ie, slowly proliferating myeloma) to attain IFE negativity than it is for patients with an immature myeloma (ie, highly proliferative myeloma). If a small amount of serum M protein remains, it is unclear whether that small amount is secreted by very few highly secreting plasma cells or by a large amount of minimally secreting myeloma cells. If we want to have a better idea of the remaining tumor load, we need techniques that can detect small amounts of abnormal cells rather than measuring the product secreted by these abnormal cells."http://www.clinicaladvances.com/article_pdfs/ho-article-200702-tricot.pdf
Additionally, the differentiation here between mature vs immature myeloma cells also likely accounts for how we see rapid relapse in patients with cytogenetic abnormalities. Thus, it makes it even more important to have tests that measure tumor load vs surrogate testing of the
paraprotein. I suspect that this also likely explains why someone can have extensive bone damage from the multiple myeloma and yet bounce back very well (having mature myeloma) vs someone who may have little bone damage and yet have far more aggressive disease (immature myeloma). As well as that would account for a mature myeloma patient having a PR that is sustained vs an immature myeloma patient having a CR that rapidly relapses, because the CR would be based on surrogate paraprotein vs tumor load. These differences in pathogenicity of the disease relative to how outcomes are being measured in trials have been baffling me for quite some time. It was nice to learn plausible causes of the disparity between test outcomes and overall survival , in clinical trials, is far more likely due to the what the tests are measuring than to 'high risk' which while categorized by cytogenetics, simply means higher proliferation.
IOW's if a person has immature myeloma, they would likely benefit from more than the traditional 8 cycles to drive down tumor burden as well as having a PCR test that would confirm the tumor cellular burden vs tests which measure the paraprotein. This is consistent with other trial analyses where they found that rapid decline in B2 microglobulin within 2 cycles correlates with rapid relapse. It makes complete sense if the secretory paraprotein is what has been measured.
Additionally, in the same article you cited..
"A remarkable finding of this study was that the quantitative PCR defined 7 patients with hematologic CR in the bad-prognosis group, whereas 12 of the 43 patients who achieved only a partial hematologic remission were assigned to the good-prognosis group. These findings strongly suggest that the amount of paraprotein remaining after high-dose therapy is not an accurate reflection of the remaining tumor load"
Which again would account for PR's having greater PFS than CR's.
All of which makes me wonder whether we are doing justice to patients in terms of the parameters that are being used to measure clinical trial outcomes. Yes, the PCR tests are expensive, and laborious BUT it is far more important to have an accurate assessment of the disease status than to simply be able to measure RESPONSES and having established that as a criteria for efficacy and outcomes just doesn't seem scientifically ethical.
With regard to mobilization of stem cells and MRD the article gave reason to pause about apheresis, in terms of the likelihood of collecting more multiple myeloma cells:
"Using the same technique, we subsequently demonstrated a differential mobilization between myeloma cells and hematopoietic progenitor cells.21 The highest proportions of immature hematopoietic progenitors were collected during the first 2 days, whereas peak myeloma cells were collected on days 5 and 6 of apheresis. In addition, the myeloma cells found in the collections on days 5 and 6 showed a higher labeling index"
If I am understanding this correctly, this means that you collect aggressive rapidly proliferating primitive cells the first two days you are on apheresis??
Overall, I hope that as we move towards more Precision Medicine, it results in clinical trials that measure disease cellular burden when measuring theraeutic outcomes. That is the way for patients to truly get some measure of stability with regard to their disease and for us to move toward multiple myeloma being a chronic if not curable disease.
These surrogate tests though are an injustice...too much false hope.
I can always rely on you to provide articles with more in-depth information, lol. That's a good thing. As I did learn that F-PCR works for 91% of multiple myeloma patients.
http://www.ncbi.nlm.nih.gov/pubmed/18637804
I soo agree about LeBron missing Bosh. I was happy to see him return it makes a big difference. I like DeWayne Wade and he has an awesome game, but he won a championship with Shaq and has not carried a team on his own. Last year the Heat had to make a transition and now I hope the trio has their timing and roles down better as LeBron is the only one who has ever carried a team on his back and he showed that again in game 7 with Celtics. I think he is ready to carry the Heat all the way to a ring this year!!...but OK Thunder is hungry and young..so this should be a great Finals Series. I hope you are right that the Heat take it all.
The article you linked to on PCR was quite informative for a number of reasons while I found the answer, to how the PCR test is performed in another article,(Gonzalez 2003) which boils down to testing technique and probe failure due to greater mutation rates, as:
.. these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (multiple myeloma) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells....snip..Usually, allele-specific oligonucleotides (ASO) are targeted to the VDJH junction and the TaqMan probe and reverse primer are targeted to JH consensus and intronic regions. In this situation, it is possible that the consensus primers and probe coincide with a somatically mutated JH segment. If this happens, the primer and/or probe will be mismatched and PCR efficiency will be dramatically reduced."
http://www.ncbi.nlm.nih.gov/pubmed/12764368
The mutational difference then for multiple myeloma is highlighted due to PCR techniques not encountering this issue in diseases like leukemia/lymphoma that are characterized primarily by a single mutation that accounts for the disease.
It was the other information that was of far greater value in terms of understanding multiple myeloma pathogenesis.
I have consistently been baffled in terms of PR's and CR's where the former has longer PFS.despite knowing hematologic tests are surrogate tests for multiple myeloma What the article, you cited, made clear is that this is due to measuring paraprotein vs cells.
Ultimately tests such as IF, SPEP, etc are reliant on secretory rates of the multiple myeloma cells which of course varies from patient to patient and is not prognostic for disease aggressiveness. That had been such a big disconnect, when you have a patient classified ISS stage I but yet instill, clinical trials show due to cytogenetics the outcomes are dismal. This of course is due to measuring RESPONSES vs disease cellular load. Whereas, quantitative tests measuring the actual number of cells present gives a far more accurate and sensitive measure of the disease status. Particularly, as it pertains to disease progression rates along with relapses. Thanks to the article you cited, at least, I have an answer to that conundrum finally:
"Although IFE can detect even small amounts of M protein of at least 5 mg/dL, measuring
M proteins is a very poor technique to estimate the remaining tumor load. This technique would be reliable if all myelomas secreted the same amount of immunoglobulin per cell and per day; however, there is a large interpatient and intrapatient variability in immunoglobulin secretion per cell per day. In general, the more mature plasma cells secrete a larger amount of immunoglobulin per day than the immature plasma cells.8 Therefore, it may be more difficult for patients with a mature-appearing myeloma (ie, slowly proliferating myeloma) to attain IFE negativity than it is for patients with an immature myeloma (ie, highly proliferative myeloma). If a small amount of serum M protein remains, it is unclear whether that small amount is secreted by very few highly secreting plasma cells or by a large amount of minimally secreting myeloma cells. If we want to have a better idea of the remaining tumor load, we need techniques that can detect small amounts of abnormal cells rather than measuring the product secreted by these abnormal cells."http://www.clinicaladvances.com/article_pdfs/ho-article-200702-tricot.pdf
Additionally, the differentiation here between mature vs immature myeloma cells also likely accounts for how we see rapid relapse in patients with cytogenetic abnormalities. Thus, it makes it even more important to have tests that measure tumor load vs surrogate testing of the
paraprotein. I suspect that this also likely explains why someone can have extensive bone damage from the multiple myeloma and yet bounce back very well (having mature myeloma) vs someone who may have little bone damage and yet have far more aggressive disease (immature myeloma). As well as that would account for a mature myeloma patient having a PR that is sustained vs an immature myeloma patient having a CR that rapidly relapses, because the CR would be based on surrogate paraprotein vs tumor load. These differences in pathogenicity of the disease relative to how outcomes are being measured in trials have been baffling me for quite some time. It was nice to learn plausible causes of the disparity between test outcomes and overall survival , in clinical trials, is far more likely due to the what the tests are measuring than to 'high risk' which while categorized by cytogenetics, simply means higher proliferation.
IOW's if a person has immature myeloma, they would likely benefit from more than the traditional 8 cycles to drive down tumor burden as well as having a PCR test that would confirm the tumor cellular burden vs tests which measure the paraprotein. This is consistent with other trial analyses where they found that rapid decline in B2 microglobulin within 2 cycles correlates with rapid relapse. It makes complete sense if the secretory paraprotein is what has been measured.
Additionally, in the same article you cited..
"A remarkable finding of this study was that the quantitative PCR defined 7 patients with hematologic CR in the bad-prognosis group, whereas 12 of the 43 patients who achieved only a partial hematologic remission were assigned to the good-prognosis group. These findings strongly suggest that the amount of paraprotein remaining after high-dose therapy is not an accurate reflection of the remaining tumor load"
Which again would account for PR's having greater PFS than CR's.
All of which makes me wonder whether we are doing justice to patients in terms of the parameters that are being used to measure clinical trial outcomes. Yes, the PCR tests are expensive, and laborious BUT it is far more important to have an accurate assessment of the disease status than to simply be able to measure RESPONSES and having established that as a criteria for efficacy and outcomes just doesn't seem scientifically ethical.
With regard to mobilization of stem cells and MRD the article gave reason to pause about apheresis, in terms of the likelihood of collecting more multiple myeloma cells:
"Using the same technique, we subsequently demonstrated a differential mobilization between myeloma cells and hematopoietic progenitor cells.21 The highest proportions of immature hematopoietic progenitors were collected during the first 2 days, whereas peak myeloma cells were collected on days 5 and 6 of apheresis. In addition, the myeloma cells found in the collections on days 5 and 6 showed a higher labeling index"
If I am understanding this correctly, this means that you collect aggressive rapidly proliferating primitive cells the first two days you are on apheresis??
Overall, I hope that as we move towards more Precision Medicine, it results in clinical trials that measure disease cellular burden when measuring theraeutic outcomes. That is the way for patients to truly get some measure of stability with regard to their disease and for us to move toward multiple myeloma being a chronic if not curable disease.
These surrogate tests though are an injustice...too much false hope.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
28 posts
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