I participated in an hour long panel discussion yesterday, featuring Dr. Ravi Vij, a myeloma and transplant expert from Washington University in St. Louis, along with a half dozen other patients and caregivers.
Sponsored by TrialX, this Multiple Myeloma Cure Panel broadcast was the first of what I hope to be many teleconference style discussions about topics which concern multiple myeloma patients and caregivers.
The audio wasn’t the best, but some interesting questions were raised. For example, I asked about dexamethasone and optimal dosing. Getting Dr. Vij to admit that researchers aren’t even sure what the average optimal dose is–let alone for an individual patient–was telling.
Dr. Vij responded that researchers are concentrating on keeping patients alive longer, so too many quality of life issues are put “on the back burner.”
I asked if 40 mg of dex had proven to be an optimal dose. Then I asked if researchers knew when it was best to take each dose. Dr. Vij’s short answer: “No.”
Our good friend and Purdue researcher, Gary Blau, would have dropped his phone if he were listening!
For those of you who haven’t been following along regularly, Gary and his Purdue University colleagues, have developed a way to answer these very important questions.
Just imagine how much better our quality of life would be if we knew the answers to these dosing questions. And our doctors would probably get better results from the therapies they are using, too!
I didn’t actively promote the broadcast because I wasn’t sure how well it might work.
A few bugs aside, I felt the hour was very worthwhile. I have interviewed Dr. Vij in the past. One great thing about him is he isn’t afraid to answer a question openly and honestly.
My old friend, fellow myeloma blogger Nick Van Dyk, participated as well. But while I was focused on day-to-day, quality of life issues, Nick reminded me that Dr. Vij opened with a startling pronouncement.
According to Dr. Vij, as many as 10% of people treated with newer novel therapy agents in combination with an auto transplant “look like they might be cured.”
Wow, Nick! Guess I buried the lead! Here I’m worried about better ways to deal with dex, and our guest doc was talking about a cure!
I am looking forward to learning and sharing more with my fellow patients on future broadcasts. I promise to let you know when that is–and how you can access each program.
Feel good and keep smiling! Pat
August 23rd, 2012 at 11:41 am
I don’t think you buried the lead, Pat. It’s kind of hard to get excited about 10%. Isn’t that about the percentage that lived for 20 years with MM with treatments before the novel agents?
August 23rd, 2012 at 12:30 pm
I was a listener at the Cure Talk yesterday and despite the mentioned audio problems I thought it was definitely worthwhile. Your voice was great and came through loud and clear! When Dr. Vij mentioned the 10% my jaw dropped, and the remainder of the hour I kept hoping someone would ask him, “Who are these lucky 10%ers?” If you ever find out, Pat, please let all os us know!
August 23rd, 2012 at 3:20 pm
I thought it was less than 5%, Joseph. But you make an excellent point. It’s like patient who gets radiation and chemo, then starts a nutritional program and their colon cancer disappears. They are all excited that the nutrition did it., But some patients go five years with no treatment. More with therapy. Just nutrition? They could be one of the patients who do well with no treatment…
August 23rd, 2012 at 3:24 pm
I have gotten emails and facebook inquiries about that, Beth. Most likely a borderline smoldering patient and doctors hit them hard upfront and most – if not all – myeloma clones are destroyed. BUT. How/why did they get it in the first place? That genetic abnormality still exists, know what I mean? But I guess in that case ten years out you could consider them “cured.” Not exactly a “shoot-off-the-fireworks” type of thing! Sorry. But I’m more skeptical about “cure” than some. But I’m more optimistic that chronic “cure” that might help 20-30% of patients is less than five years away…
August 23rd, 2012 at 4:25 pm
I got a chance to check in on the blog today. I have not had time to listen to the panel. I will check it out when I get back from my trip. That 10% figure is nothing unexpected. Let me show an old long term Canadian study comparing autos to allos. It was published in 2007, so the patients were treated in the 90′s. No novel agents for either group. Here is the long term followup:
“The overall survival (OS) of the alloSCT cohort was 48.1% at 5 years and 39.9% at 10 years compared to 46.2% at 5 years and 30.8% at 10 years for the ASCT cohort (P=.94). The event-free survival of the alloSCT cohort was 33.3% at 5 years and 31.4% at 10 years compared to 32.9% and 15.2% for the ASCT cohort (P=.64). Treatment-related mortality (TRM) at 1 year was 22% for the alloSCT cohort and 14% in the ASCT cohort (P=.21).”
http://www.ncbi.nlm.nih.gov/pubmed/17640596
You probably do not agree with me, but usually I would expect the rate of relapse to be fairly steady. In the previous 5 years in the study half the auto patients relapsed (32.9% to 15.2%). If half relapse in the next 5 years that leaves 7.6% not relapsed at 15 years. I would like to think that the novel agents could raise that to 10%. As Dr. Bensinger, Alsina, Rajkumar and Anderson (and me!) would expect, the allo patients relapse rate is only from 33.3% to 31.4% between years 6-10. It is not zero, but I would think that that low relapse rate after year 5 is as good as it gets for myeloma patients given the therapies available in 2012. Is this study an example of what you would call “chronic cure” for the allo patients treated back in the 90′s?
August 23rd, 2012 at 4:57 pm
I love the way Mark interjects allo-related info into our discussion! Keep it up, Mark! But in this case, I believe that Dr. Vij was referring to a lucky 10% that has done unusually well while using novel therapy agents after an auto stem cell transplant. That means even more patients may be “cured.”
August 24th, 2012 at 12:56 am
Hi Pat,
Thank you very much for being part of our first Myeloma Cure Panel. It was a pleasure to have you. The link to the audio of the panel discussion is http://trialx.com/curetalk/2012/08/thank-you-for-your-support-myeloma-cure-panel-talk-show-team/.
Thank you once again. Priya
August 24th, 2012 at 10:33 am
Thanks, Priya! Let’s do it again! Lots of controversial and thoughtful topics we could explore. Glad to help!
August 28th, 2012 at 11:46 pm
I just got a chance to listen to the Cure Panel. That was really interesting. One point I would make as a follow up to our long discussion after the JQ1 article is that I found it interesting that Dr. Vij brought allogeneic transplantation up a couple of times and none of the patients brought it up. It goes back to my point as to why I think they should not spend any more research time on allos in the myeloma community. There is almost no patient interest in the procedure. We get plenty of info on allos from the research done in other blood cancers. Allos are not meant to be used as the therapy of last resort as most myeloma patients want to use them.
I really found the answer to your question eye opening. There is so little consideration by the Doctors about a patients QOL. If I could have sat in my question would have been a great a follow up to yours. I was going to point out that I did very aggressive therapy for 8 months but I have been off all therapy for 15 months and my QOL is really good. That is the exact opposite of the “new paradigm” of continuos therapy (mine included two high doses of melphalan, a high dose of fludarabine, and double doses of Velcade and Doxil during induction) and it is clear from the Blogs I read that few patients have as good of a QOL as I do. Why is it that the continuos therapy model is being so widely adopted when there is no evidence that maintainence therapy increase Overall Survival?
It would not have been appropriate to mention it in that setting, but even the trial that Dr. Vij says shows an increase in OS with never ending Revlimid therapy, the OS curve actually starts to go in favor of no maintenance at about 70 months. I think the perception on a lot of patients part that high dose therapy leads to poor QOL in the long term is way off base. It is the continuos therapy model that seems to lead to poor QOL and it does not seem to improve OS. This seems like common sense to me what this study showed:
‘While the impact of various treatments on myeloma patients’ health-related quality of life (HRQL) has been reported, the impact of a treatment-free interval (TFI) is currently unclear. The aims of this study were to assess if (1) a TFI is associated with a better HRQL vs. other treatment phases and (2) the length of the TFI influences HRQL.”
“Patients enjoy better HRQL when in their first TFI, and the length of the TFI also positively impacts on HRQL This information may be important for patients and their physicians making treatment decisions and has implications for treatment protocols incorporating extended therapy.”
http://www.ncbi.nlm.nih.gov/pubmed/22886429
August 29th, 2012 at 9:49 am
Very insightful, Mark. I am going to do several reader comment follow-up posts over next few days. I will address several of your points then. In the meantime, Check-out today’s post. Dr. Bradner gives us an update about JQ1…
August 31st, 2012 at 1:48 pm
Wow this is great progress—”According to Dr. Vij, as many as 10% of people treated with newer novel therapy agents in combination with an auto transplant ‘look like they might be cured.’”
August 31st, 2012 at 5:51 pm
Yes, but it’s complicated. (Why is there always a “but?”) Only ones with hope for a cure would be low risk, newly diagnosed patients that undergo multiple transplants and a heavy post chemo regimen for three or four years. Still, what concerns me is this option is rarely given to such patients unless they happen to go to UAMS or maybe Huntsman. We need to get the word-out about that! Because there is a possibility that over 50% of such patients could be “cured,” or at very least remain in CR for at least a decade…
September 1st, 2012 at 11:23 am
I think you may be overestimating the percentage of patients that get long term disease free survival in “total therapy”. From what I understand, the percentage of low risk patients that get to CR in “total therapy” is around 60%. Those graphs they show are only showing the 60% or so that get to CR, not the entire “low risk” group. Also, in 2010 when UAMS was showing TT 2 results, they were not showing all the patients in the graphs that were published in the Journals showing TT data. Dr. Mehta used to work at UAMS and he picked up on this:
“Another weakness is the lack of direct information on fatal treatment-related toxicity in any of the published articles that report on the Total Therapy 2 trial. Figure 2B in the article by Barlogie et al1 shows that a total of 287 patients have died, and Figure 2D shows that 159 patients have died after experiencing disease progression. This suggests that 128 of 668 patients (19%) died as a result of nonrelapse causes. If true, this indicates that the treatment approach is prohibitively toxic. If the 19% estimate that I derived on the basis of available data is incorrect, the entire analysis and data set need to be revisited for possible inaccuracies, not only for this article but for all publications pertaining to the Total Therapy 2 trial.”
http://jco.ascopubs.org/content/29/5/e124.full
It turns out the non-relapse mortality was 14% (Figure 1 )and those patients were not included in the graphs. The 14% is the combined number of treatment related mortality and cause of death unknown. It is a lot easier to make your data look good when your are not including between 14 – 19% of the patients that have poor outcomes in them.
http://jco.ascopubs.org/content/29/5/e125.full
September 1st, 2012 at 3:01 pm
I can’t believe that I’m going to defend TT. I’m more of a “do as little and take as little as possible to do the job” kind of guy. But a couple of things. First, there are dozens of different studies and graphs and trends and charts. Like in politics, supporters pull-up the ones that best make their case. Nick in California believes Dr. Barlogie when he says that if you remain in CR for three years after your five years of therapy are up, you have a 98% chance you are cured. I tried arguing, but Nick interprets things so differently than I do, we don’t get anywhere. I will say this. They do have pretty impressive ten year results. Cure or no cure, someone might want to gamble with a lot of extra meds in order to maybe be cured. Of course, the counter argument to all of this is a newly diagnosed low risk patient probably has a ten year median life expectancy now, too. Nick believes he’s cured. Are you going to take that away from him, Mark? I am working on a expose’ about TT. Going to take me five or six months to put together in my “spare time.” One more thing. You talk about outcomes. I don’t think Nick is including subjects that die of something else. The point is “you won’t die from multiple myeloma,” so others don’t count! They have a point – unless TT contributed to their dieing from something else!
September 3rd, 2012 at 9:36 am
UAMS definitely has the best marketing department, that I am sure of. I was trying to explain why everyone is not offering “total therapy”. What statistic are you refering to when you say 50% of the low risk patients may not relapse in 10 years?
What you are reading on Nick’s blog is typically the good SUBGROUP that Nick is in. I believe the percentage of patients that get to CR is around 60%. That means around 40% of the low risk patients are not on the graph. Some of the patients lose CR early. I pointed out an example where they pulled 19% of the patients of the patients with bad outcomes off their graphs. When I have seen OS graphs of the whole group they do not look any better than any other Centers data and they do not appear to show a plateau which would indicate cure. Page 5 shows the OS of TT3. In the subgroup Nick is in, the graphs do look great (page 16). I think more of the Doctors read the data like I do, which is to say that the subgroup of patients like Nick is a smaller portion of the group than you seem to think they are.
http://www.comtecmed.com/costem/2011/Uploads/assets/16_barlogie.pdf
September 3rd, 2012 at 1:52 pm
Mark, you are going to have to slug this one out with Nick. I didn’t make a dent! He is adamant that 98% of TT CR patients that make it past three years are cured. So you are right, that is a smaller sub-group of patients. He isn’t talking about how many reach CR. For him, it’s how many stay in sustained CR. That’s the “Holy Grail” that other low risk patients might try and achieve. I am currently doing a lot of research about all of this. But I can see TT does sustain CR for longer periods of time than any therapy I’m aware of – if you are one of the ones who reach the three years, of course. So again, why isn’t this given as an option – along with donor transplants – to newly diagnosed patients? Because like TT, allo transplants work best early, right?
September 5th, 2012 at 10:02 pm
Pat, Hell did freeze over! You defending Total Therapy?? Pat and Mark, sorry I am getting into the discussion late, but you certainly got a great conversation going. When I saw the discussion, I went back to the source document for TT2 at the following link: http://jco.ascopubs.org/content/28/18/3023.full.pdf What I saw was that they show the death rate of 287/668 or 42% at 8 years (Figure 1 Graph A).Therefore overall survival including all deaths is 58%.
I did not find Mark’s number of 128 or 19% of the patients dying from non myeloma causes, but based on the Social Security death rate tables one would expect the total normal death rate from all causes for the average 70 year old would be 24.1%. 70 is the average age of a myeloma patient. So the 19% seems high but is actually 5.1% better than the expected rate. The Social Security tables are at the following link: http://www.ssa.gov/oact/STATS/table4c6.html
The National Cancer Institutes SEER data would give an 8 year survival rate of 25.2%, however this is Relative Survival(which excludes non myeloma deaths). Therefore comparable data for TT2 would be 58%+19% or 77%. So TT2 data would suggest that you will be 3 times more likely to survive with the TT2 protocol than at the average SEER facility. The TT3 program has a much better survival rate. I hope this helps to provide another view of these findings.
Best Regards/Gary
P.S – I enjoyed working with you on the CureTalk panel.
September 5th, 2012 at 11:48 pm
Thanks much for your analysis, Gary! Nick would argue these stats are misleadingly LOW–and that many of those that survive are possibly cured–even more so for TT3. But TT by any name or number is a tough road to travel. Multiple myeloma is a unique cancer in that patients are forced to make life and death choices before they are ready or prepared to do so. Tough stuff…
September 6th, 2012 at 11:50 am
Pat, Gary,
Great discussion. Both of you perform a great service with your blogs. I really think a patient could learn more from reading our discussions than they can listening to a panel discussion of myeloma Doctors!!!
Mark
September 6th, 2012 at 12:52 pm
Thanks, Mark! Not sure about the “more than myeloma doctors” part, but that’s the idea…
September 6th, 2012 at 1:56 pm
Pat, it is tough and just 5 or 6 years ago it was “you will die in 3 years!so get prepared! Now some are talking cure. Barlogie at 60% for the 85% that are low risk, and Dr. Vij who is saying that novel therapies will provide a 10% cure. We may just outlive this death sentence!!! Mark, thanks for the kind works, and I must say you sure did help to get a lively discussion going. Best Regards/Gary
September 6th, 2012 at 2:45 pm
I’m starting to think it’s possible, too! My only concern: Will my body hold-up long enough. Drugs might kill us before myeloma does!
September 24th, 2012 at 7:57 pm
Pat,
I saw another reference to all the “unknown” cause of deaths in the “total therapy” trials.
“In historical times, when someone died of a cause that doctors didn’t understand, they just put “natural causes” or “unknown” on the death certificate. As modern medicine advanced, and we began to understand and diagnose more diseases, fewer people officially died of unknown causes; the real cause of death was recorded instead. This trend has continued for decades, if not centuries.
Unless you happen to die while on a clinical trial in Arkansas…
A group at the University of Arkansas for Medical Sciences, called the Myeloma Institute for Research and Therapy (MIRT), has a rather shocking rate of deaths attributed to “unknown causes” in their clinical trials. The parallels to the Vioxx case, in which an unusually high number of deaths were classified as due to “unknown” causes, should be cause for alarm.
As outlined in this exhaustive analysis sent to us, across a series of clinical trial publications, the proportion of deaths due to unknown causes is 25-37% for patients in MIRT trials, versus around 6-16% in a variety of similar clinical trials at other institutions…”
http://www.science-fraud.org/?tag=barlogie
Mark
September 24th, 2012 at 10:20 pm
Thanks, Mark. This is a fair debate, but let’s keep it “clean.” I can understand why a UAMS (correct acronym) patients might be offended by the tone of the Science Fraud post–even though there may be some truth in the content. Both M.D. Anderson and UAMS have been accused of this sort of thing over the years. I have no way to know how valid the criticism is. But I would like to argue–no, let’s say actively discuss–the cure vs control issue from time to time. I’m a proponent of what I call a “chronic cure.” In a way, Total Therapy is a perfect example of this.
September 25th, 2012 at 10:11 pm
I thought todays blog post was going to be a rant about the officiating in the Packers game last night!
Did you check any of the links in the article? I am surprised Blood published the letter Dr. Mehta sent in. Dr. Mehta used to work at UAMS. I do not think I have ever seen a well known myeloma Doctor write anything like this about another institution.
“Patients enrolled on studies in Arkansas have an unusually high propensity to die of “unknown” or “indeterminate” or “other” causes. This happened to 13% of all participants (corresponding to 29% of all deaths) in the Total Therapy 2 study [1] and to 8% of all participants (corresponding to 30% of all deaths) in the Total Therapy 3 study [2]. Indeed, 13% of all patients with smoldering myeloma (corresponding to 56% of all deaths) who received thalidomide died of “unrelated” causes [3] that remain unclear [4]!
These mystery deaths are oddly out of keeping with the statement in their latest work looking at second malignancies [5]: “This uniform stringency in therapy and subsequent patient follow-up is a hallmark of the TT trials program and has afforded the investigators to make many clinically meaningful and novel observations.”"
“I am also curious to know if all these unusual occurrences have been reported to the local IRB and the FDA (since the studies were conducted under INDs) – and would like to know what their suggestions were to reduce “unknown” deaths.”
http://bloodjournal.hematologylibrary.org/content/early/2012/06/06/blood-2012-04-421883/reply#bloodjournal_el_7088
I bet Dr. Mehta would like to contribute to your expose!!!
September 25th, 2012 at 11:08 pm
The post/article was borderline, don’t you think? But where there’s smoke…