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!