I'm waiting for BB to get back to me with more specifics. For a couple of reasons, I'm not going to post about this for the next few weeks. As of now, though, I'm fine. Complete remission as of last week's very sensitive tests. Onward!
Friday, July 25, 2014
Monday, July 21, 2014
Good, bad and ugly
I'm pretty sure I've used that reference before here. In fact now that I think about it, I remember feeling sorry for Eli Wallach. I can picture his agent calling him. "Eli, baby, have I got a part for you! There's this movie, see, called The Good, The Bag and The Ugly. The parts of The Good and The Bad have already been cast…"
The Good
What a handsome devil, eh?
So the good news is that my tests last week came back negative for MRD (clean bone marrow) and my numbers look really, really good.
The Bad
A tough customer indeed, is Mr. Van Cleef. As another "Van", by the way, I have no idea what a "Cleef" is. A Dutch pronunciation of Cliff? Hmm.
The bad news is that the MRI is unchanged. Stable, faint, sub 1cm focal lesions (not currently active for cancer) are still seen at T2, T3, T4, T10 and T12. I like the faint part, I suppose. I sure wish they would go away, though, for reasons which will shortly become apparent to readers that see this post through to its conclusion. As was published by Arkansas just last week (more on this below) these lesions can be issues because "MRD…only evaluates a random marrow aspirate and does not assess any dormant consecratory myelomatous cells, which can be present in focal lesions on magnetic resonance imaging (MRI), and can provide a disease reservoir for relapse."
In other words, as I have reported from time to time in this blog, I want those bloody things gone.
The Ugly
Yes…well…forgive me if I feel more sorry for myself than Eli after all. Get a load of these graphs, from this article just published by UAMS about how stem cell transplants are curing people.:
Recall I was in the "TT4 Lite" arm of the study. This can be most readily identified as the lines as the bottom were people are relapsing left and right without any indication of a plateau.
Specifically, TT4 patients with deletion 13 and hypo diploid disease (that's too few chromosomes versus too many -- and it's odd because too many chromosomes is generally a better prognosis) have done well and reached a plateau after two years. However the other cohorts in TT4 Lite have no fared well at all. For this with no cytogenetic abnormalities, if this graph is right (and there may be an error in it since there appears to be a cliff at the 5.5 year mark and it suggests something's wrong with the graph selection) there's no plateau and the relapse rate is high with only 30% of people still in CR at the 5.5 year point. Looking at it objectively, I think there must be a mistake in the graph…so maybe I feel a *little* better if that's the case (I've asked my friends at UAMS to clarify) but still, it looks like the Lite arm isn't faring nearly as well as the Standard arm. Did I sell my therapy short? Should I have gone through something more rigorous? Should I go through something more rigorous right now?
We'll see what they have to say.
I do feel like the goalposts keep being moved farther and farther back. Can I make it another five years in complete remission and breathe easy? That's a lot of waiting…
It's ugly.
The Good
What a handsome devil, eh?
So the good news is that my tests last week came back negative for MRD (clean bone marrow) and my numbers look really, really good.
The Bad
A tough customer indeed, is Mr. Van Cleef. As another "Van", by the way, I have no idea what a "Cleef" is. A Dutch pronunciation of Cliff? Hmm.
The bad news is that the MRI is unchanged. Stable, faint, sub 1cm focal lesions (not currently active for cancer) are still seen at T2, T3, T4, T10 and T12. I like the faint part, I suppose. I sure wish they would go away, though, for reasons which will shortly become apparent to readers that see this post through to its conclusion. As was published by Arkansas just last week (more on this below) these lesions can be issues because "MRD…only evaluates a random marrow aspirate and does not assess any dormant consecratory myelomatous cells, which can be present in focal lesions on magnetic resonance imaging (MRI), and can provide a disease reservoir for relapse."
In other words, as I have reported from time to time in this blog, I want those bloody things gone.
The Ugly
Yes…well…forgive me if I feel more sorry for myself than Eli after all. Get a load of these graphs, from this article just published by UAMS about how stem cell transplants are curing people.:
Recall I was in the "TT4 Lite" arm of the study. This can be most readily identified as the lines as the bottom were people are relapsing left and right without any indication of a plateau.
Specifically, TT4 patients with deletion 13 and hypo diploid disease (that's too few chromosomes versus too many -- and it's odd because too many chromosomes is generally a better prognosis) have done well and reached a plateau after two years. However the other cohorts in TT4 Lite have no fared well at all. For this with no cytogenetic abnormalities, if this graph is right (and there may be an error in it since there appears to be a cliff at the 5.5 year mark and it suggests something's wrong with the graph selection) there's no plateau and the relapse rate is high with only 30% of people still in CR at the 5.5 year point. Looking at it objectively, I think there must be a mistake in the graph…so maybe I feel a *little* better if that's the case (I've asked my friends at UAMS to clarify) but still, it looks like the Lite arm isn't faring nearly as well as the Standard arm. Did I sell my therapy short? Should I have gone through something more rigorous? Should I go through something more rigorous right now?
We'll see what they have to say.
I do feel like the goalposts keep being moved farther and farther back. Can I make it another five years in complete remission and breathe easy? That's a lot of waiting…
It's ugly.
Tuesday, July 8, 2014
A gold mine of information today!
It was a very productive panel discussion today with Dr. Tiedemann. There were a lot of important insights, some of which may be controversial but what the heck, let's have fun. My notes, unfortunately, were eaten by my computer here so this is from memory. I encourage you to listen back to the broadcast.
* Myeloma progenitor cells are immature cells that are more evolved than stem cells (which can form any type of blood) and are "on their way" to becoming plasma cells, but have not yet become plasma cells
* These immature cells do not express a particular protein which is associated with immunoglobulin expression. Implication #1: non-secretors probably have these cells moreso than mature plasma cells.
* We don't know whether or not these immature cells start out with cytogenetic abnormalities, or the plasma cells that they become later develop those abnormalities
* Because these cells do not express a particular protein, he believes that proteasome inhibitors are not able to kill them. Implication #2: a regimen based solely on Velcade or Carfilzomib will not cure the disease, full stop.
* He notes that cells which are resistant to treatment by IMIDs (Revlimid, Pomalidomide, Thalidomide) also fail to express a different protein. It is unclear whether or not these drugs are killing progenitor cells or merely suppressing their ability to spawn more cells. Implication #3 and it's a biggie…we don't know for sure, but if these drugs are not killing progenitor cells, then a regimen based solely on novel agents will not cure the disease, full stop. This is a big deal for doctors that espouse the "well, novel agents might work just as well as transplant."
* When asked what types of medicines DO kill the progenitor cells, he said that there was a belief that high dose melphalan (transplants) do, and that anthracyclines (like adriamycin) might but we don't know.
* He volunteered (I didn't even say the word "cure", promise) that some patients were being cured, and that those who experienced the best results likely used both novel agents (to kill the more mature plasma cells which are capable of self-replicating and after all do need to get killed!) and high dose melphalan (to kill the progenitor cells). Implication #4: sounds a lot like Total Therapy.
* I asked him whether or not that cytogenetic abnormalities that reflect disease that doesn't respond that well to transplants were observed in progenitor cells or only in the more mature cells -- he said they were researching this now, but did not know. He also said it was a really good question. I felt like I did my job today! ;)
* Importantly (I was going to ask this but someone else did, thankfully), the topic of MRD tests came up and he affirmed that multi flow cytometry tests for MRD likely WOULD show progenitor cells because even though they don't express the one kind of protein required for a protease inhibitor to latch on to them, they do express other proteins that trigger identification under sensitive MRD testing in the marrow. He did say that there was (only a) theory that some types of cells wouldn't show up, however the progenitor cells turn into plasma cells in "a matter of a couple of weeks" and therefore an MRD test done a couple of weeks after treatment should show the presence of progenitor cells if there are any kicking around.
I am puzzled by this last phenomenon because of the recurrence of the disease in high risk patients under Total Therapy. Evidently per other information shared by Dr. Usmani (formerly of Arkansas), at least some of these HRMM patients test MRD negative at some point -- yet they experience relapse. If that's the case, what is MRD missing? Is it simply that bone marrow is spotty and it could be clean in one place and not clean in another? Or is MRD not sensitive enough? I have something to ask Bart when I see him next week.
I also have to say -- and I don't like politicizing this blog but it's too topical not to -- that people who pine for Canada's health system aren't MM sufferers. Revlimid still is not available to the newly diagnosed. There isn't nearly the investment in clinical trials or the ability to enroll in one in Canada. "It's not like the US," as the good doctor said. Look, there are no easy answers to the healthcare crisis -- but when it comes to treatment for this disease, I for one am glad that we have the big horrible system that we have here. :)
And that, my friends, constitutes one very informative session. And I got a doctor to -- without me soliciting it -- say that patients are being cured. :) "Just not nearly as many as we would like." That's the God's honest truth right there.
Let's keep the research coming, folks!
* Myeloma progenitor cells are immature cells that are more evolved than stem cells (which can form any type of blood) and are "on their way" to becoming plasma cells, but have not yet become plasma cells
* These immature cells do not express a particular protein which is associated with immunoglobulin expression. Implication #1: non-secretors probably have these cells moreso than mature plasma cells.
* We don't know whether or not these immature cells start out with cytogenetic abnormalities, or the plasma cells that they become later develop those abnormalities
* Because these cells do not express a particular protein, he believes that proteasome inhibitors are not able to kill them. Implication #2: a regimen based solely on Velcade or Carfilzomib will not cure the disease, full stop.
* He notes that cells which are resistant to treatment by IMIDs (Revlimid, Pomalidomide, Thalidomide) also fail to express a different protein. It is unclear whether or not these drugs are killing progenitor cells or merely suppressing their ability to spawn more cells. Implication #3 and it's a biggie…we don't know for sure, but if these drugs are not killing progenitor cells, then a regimen based solely on novel agents will not cure the disease, full stop. This is a big deal for doctors that espouse the "well, novel agents might work just as well as transplant."
* When asked what types of medicines DO kill the progenitor cells, he said that there was a belief that high dose melphalan (transplants) do, and that anthracyclines (like adriamycin) might but we don't know.
* He volunteered (I didn't even say the word "cure", promise) that some patients were being cured, and that those who experienced the best results likely used both novel agents (to kill the more mature plasma cells which are capable of self-replicating and after all do need to get killed!) and high dose melphalan (to kill the progenitor cells). Implication #4: sounds a lot like Total Therapy.
* I asked him whether or not that cytogenetic abnormalities that reflect disease that doesn't respond that well to transplants were observed in progenitor cells or only in the more mature cells -- he said they were researching this now, but did not know. He also said it was a really good question. I felt like I did my job today! ;)
* Importantly (I was going to ask this but someone else did, thankfully), the topic of MRD tests came up and he affirmed that multi flow cytometry tests for MRD likely WOULD show progenitor cells because even though they don't express the one kind of protein required for a protease inhibitor to latch on to them, they do express other proteins that trigger identification under sensitive MRD testing in the marrow. He did say that there was (only a) theory that some types of cells wouldn't show up, however the progenitor cells turn into plasma cells in "a matter of a couple of weeks" and therefore an MRD test done a couple of weeks after treatment should show the presence of progenitor cells if there are any kicking around.
I am puzzled by this last phenomenon because of the recurrence of the disease in high risk patients under Total Therapy. Evidently per other information shared by Dr. Usmani (formerly of Arkansas), at least some of these HRMM patients test MRD negative at some point -- yet they experience relapse. If that's the case, what is MRD missing? Is it simply that bone marrow is spotty and it could be clean in one place and not clean in another? Or is MRD not sensitive enough? I have something to ask Bart when I see him next week.
I also have to say -- and I don't like politicizing this blog but it's too topical not to -- that people who pine for Canada's health system aren't MM sufferers. Revlimid still is not available to the newly diagnosed. There isn't nearly the investment in clinical trials or the ability to enroll in one in Canada. "It's not like the US," as the good doctor said. Look, there are no easy answers to the healthcare crisis -- but when it comes to treatment for this disease, I for one am glad that we have the big horrible system that we have here. :)
And that, my friends, constitutes one very informative session. And I got a doctor to -- without me soliciting it -- say that patients are being cured. :) "Just not nearly as many as we would like." That's the God's honest truth right there.
Let's keep the research coming, folks!
Another CureTalk Panel today -- interesting stuff!
And no, for once, I won't be asking expressly about whether or not the disease is curable! :)
The guest today is Dr. Rodger Tiedemann from Princess Margaret Hospital in Toronto. Dr. Tiedemann published papers last fall in which he discussed why Velcade and other proteasome inhibitors cannot cure Myeloma. The mechanism that they impact (the proteasome mechanism) doesn't exist in the immature progenitor cells that cause Myeloma. He likened the use of these drugs to having a goat eat the weeds in your garden, but not getting rid of the roots.
This prompts a number of lines of inquiry -- if it were me interviewing him, I'd get to all of the answers. I hope the format permits it!
- How does MM originate, and what is the lifecycle of a MM cell? What are the differences between a progenitor or precursor cell, and later MM cells? Do progenitor cells carry the chromosomal abnormalities, or does that happen as MM cells proliferate and develop more "genetic chaos"?
- If proteasome inhibitors do not work on the progenitor cells, what kids of therapies do? IMIDs (Revlimid, Pomalidomide, Thalidomide)? Alkalytors (Melphalan?) Anthracyclines (Adriamycin)? Or do we have nothing that works on them? Does this vary by disease biology (for example, del17 progenitor cells are more resistant to therapy than other kinds)? Where does immunotherapy enter into the mix?
- If we have something that works on them, could treating with multiple agents get both the progenitor and the more mature cells? If this isn't the case, how does he explain people that appear to be cured?
We'll see how much of this we get to -- hopefully a lot, because it has a lot of ramifications (among them: if IMIDs don't get the progenitors either, then we know definitively that the existing novel agents alone are not capable of curing anybody -- this would put an end to one existing controversy and theory).
It should be an interesting conversation -- hope some of you can join us!
The guest today is Dr. Rodger Tiedemann from Princess Margaret Hospital in Toronto. Dr. Tiedemann published papers last fall in which he discussed why Velcade and other proteasome inhibitors cannot cure Myeloma. The mechanism that they impact (the proteasome mechanism) doesn't exist in the immature progenitor cells that cause Myeloma. He likened the use of these drugs to having a goat eat the weeds in your garden, but not getting rid of the roots.
This prompts a number of lines of inquiry -- if it were me interviewing him, I'd get to all of the answers. I hope the format permits it!
- How does MM originate, and what is the lifecycle of a MM cell? What are the differences between a progenitor or precursor cell, and later MM cells? Do progenitor cells carry the chromosomal abnormalities, or does that happen as MM cells proliferate and develop more "genetic chaos"?
- If proteasome inhibitors do not work on the progenitor cells, what kids of therapies do? IMIDs (Revlimid, Pomalidomide, Thalidomide)? Alkalytors (Melphalan?) Anthracyclines (Adriamycin)? Or do we have nothing that works on them? Does this vary by disease biology (for example, del17 progenitor cells are more resistant to therapy than other kinds)? Where does immunotherapy enter into the mix?
- If we have something that works on them, could treating with multiple agents get both the progenitor and the more mature cells? If this isn't the case, how does he explain people that appear to be cured?
We'll see how much of this we get to -- hopefully a lot, because it has a lot of ramifications (among them: if IMIDs don't get the progenitors either, then we know definitively that the existing novel agents alone are not capable of curing anybody -- this would put an end to one existing controversy and theory).
It should be an interesting conversation -- hope some of you can join us!
The Cure Panel Talk Show on
Multiple Myeloma
e Myeloma on 8 JULY 2014 @ 6:00 pm ET .
To access the teleconference :
Dial -in (718) 664-6574 approximately 5 minutes prior to the scheduled start time.
Listen to the LIVE Broadcast here:
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