Wednesday, November 4, 2009

Clarifications on the previous post

I received a comment with some good questions about the previous post from the husband of a patient battling MM, and wanted to elaborate a bit on the points I made. Please bear in mind, I am a patient, albeit an educated one, but I am not a hematoloogist or medicial clinician, so take these comments as any more definitive than an interesting jumping off point for discussing them with qualified professionals to help you form your opinion.

So, to the questions:

Question one: [In comment number one from the previous entry] you are comparing a low risk myeloma patient group receiving TT3 with the total myeloma patient group. Are there any clinical trials with low risk myeloma patient groups receiving some of the other treatment programs to compare with?

Answer: I was talking discussing this with my wife this morning (without realizing you had asked) under the heading of "why isn't everybody doing this yet." I am sure the data is out there, and eventually BB or others will probably show it to prove more definitively that his program works. He has gene array information from the people that get tested there initially and choose to go would be a matter of tracking these people to see how they fare from other treatment, and then separating those out into low versus high risk groups. Right now, on a blended basis, BB believes he can cure 74% of newly-diagnosed patients with the current protocols. The highest official figure I have heard from anybody else (with the possible exception of BB's former colleague in Utah) is 0%. That's good enough for me. Until I hear another doctor, with data to support his contention, that he can cure, say, 30% of his patients that are newly diagnosed, there's not really anything to compare to. Other people don't believe BB is able to really achieve these results. Total Therapy's results have really only been around for 2-3 years. Eventually, one hopes they will catch on.

Question two: I am not sure what number 2 is saying. I think it means the average health of the general population is pretty poor which is not surprising. You are saying that the low risk myeloma patients that have TT3 treatment will outlive the average population, amazing. I think this says more about the health of our general population than this myeloma treatment method.

Answer: I don't disagree with you that people should take better care of their health. Bear in mind, MM patients in BB's clinic are not told to stop drinking any alcohol, become a vegan, or anything like that. He counsels people to remain in good physical shape, as any physician would, because obesity is a problem for EVERYTHING.

However, since it originally took much longer for previous regimes of Total Therapy to surpass the general population, it's not really a function of otherwise healthy people not taking care of themselves. I mean that might explain some of it, but the fact that successive treatment of Total Therapy 2 or 3 demonstrate improvements while the same general population is there seems to indicate that general population health doesn't matter.

Here's the graph:

The horizontal line at 1.0 is the expected survival of the general population. You can see in Total Therapy 1, lower survival until 15 years or so. But somebody who went through Total Therapy 1 and lived for 15 years actually had a higher chance of being alive than somebody who didn't have myeloma. This is a long-term view, to be sure. But look at Total Therapy 3 -- if you make it five years (and recall, 90% of low-risk TT3 patients are in complete remission after five years at this point) you are in line with the general population, and based on the experience of both TT1 and TT2 should be superior (although the data doesn't exist yet as TT3 is only five years old).

Question 3: In number 3 I am not sure how 5 years of statistics can prove something beyond 5 years. If you live 7 years beyond start of treatment and die of another cause is that a cure? But, you would need more than 5 years of statistics. I assume the 5 years may be the collection period and it includes patients with more than 5 years of data. Do you know what percentage would be for one of the other popular treatment methods with low risk myeloma patients?

I'll answer in several parts. Without going into too much detail, if you have a trend of information for five years and it correlates with other variables, you can perform a statistical analysis called a regression that allows you to extrapolate additional information over time. Taking a very, very simple example, if you knew that 2 years ago your mortgage payment was $1,000 a month, and a year ago it was $950 a month, and this year it is $900 a month, you could accurately predict that in two years it would be $800 a month. Obviously, the Myeloma data is much more complicated than this, but the same statistical tools work with it.

If you live 7 years beyond treatment and die of another cause, in BB's data, you are counted as a fatality. Thus, to be a survivor, you have to have survived everything. That makes these statistics all the more impressive.

Total Therapy 3 was initiated five years ago, and thus there are only five years of data. There are much longer data sets for Total Therapy 1 and 2 -- the survival curves show a similar plateau after a number of years -- i.e. if you survive that long, you're probably cure. Unfortunately, in Total Therapy 1 and 2, the cure rates weren't high enough. But Total Therapy 3 -- which added Velcade, Revlimid and some other changes in therapy cadence -- has been remarkable.

This graph shows both low and high risk myeloma patients. The gold standard chart is event-free survival, which shows that after five years out, close to 80% of all TT3 folks are still alive. Compare with, over time, the survival rates of TT1 (around 25% at five years, TT2 without thalidomide (around 40%), TT2 with thalidomide (around 60%), etc. You can see the shape of the curves are relatively predictable. They key is where that plateau forms -- plateau meaning that beyond that point, if you haven't had recurrent myeloma, it won't be coming back. BB currently believes this is around 72 months from starting treatment.

For low risk disease, the data is even better.

As for the percentage survival rate for other types of therapy, nobody keeps statistics because nobody else believes the disease is curable. I was flat out told by my first hematologist, who did ultimately suggest I check out Arkansas, that he did not believe transplant even prolonged life, much less cured the disease. He is still an advocate of a transplant only because that means you can go off all therapy -- until it comes back. So they don't bother tracking this. I only know this: while the data looks back five years, so doesn't reflect the full benefit of Velcade, the American Cancer Society published last year that five year survival is 34%. Some of those people get poor care, but some also get Total Therapy. So to interpolate from that, overall survival from other methods has to be a hell of a lot lower than Total Therapy. New drugs, such as Carfilzomib and Pomalidomide, may change the game when they come out in a few years but nobody is talking about them like a cure.

Question: In number 4 are you saying the average age at diagnosis of low risk myeloma patients receiving TT3 are 71 years old. I thought it was the young and healthy myeloma patient recommended for this treatment method.

This data comes from different places. I recall hearing that the median (not to say the average) age at diagnosis of Myeloma overall was 71, however I suspect this is coming down into the 60s as more and more young people are getting the disease. BB will transplant people older than 71 and has been doing this for some time. It is another area of disagreement between him and other doctors. Here, I tend to be political correct and shy away from strongly suggesting that an older person dive into this program because (a) they might be sick from something else, (b) the treatment is not a lot of fun, and (c) there is an increased treatment-related mortality from treatment as age advances -- perhaps 3% or so. This is not trivial, but compare that against 70% mortality from the disease itself over a five year timeframe and it starts to come into focus. It's an individual choice, of course. In the case of your wife, I would probably at least get a second opinion from a myeloma specialist (if not BB himself) to discuss transplant. The woman I first consulted about Total Therapy was a patient, now cured, who was in her late 50s when she received treatment and was transplanted despite the fact that she had lupus. So he is more aggressive in transplantation than are most places.

I hope these answers are useful to you, and to your wife, as you navigate your own way through your battle. There is more hope than ever for Myeloma patients, whether it is through the Arkansas approach or through the variety of new and effective drugs that have come on the market in the last five years, and which are continuing to be developed. I hope that you have many long healthy and happy years ahead of you both.


  1. Nick, thanks for all the input. I like the graphs.

    With today's computer technology every oncologist should enter every cancer patient into a common data base. The name wouldn't have to be entered for privacy protection. Then there would be more information available concerning the different treatment options.

    My wife went into kidney failure in June of 07. They said they checked for myeloma but I think they only looked for the M-spike. She is a non secreter. Her myeloma cells don't make the immunoglobulins since they secrete light chain proteins only. The Nephrologist diagnosed her with some kidney desease. Now we know she had MM at that time and may have had it for several years. He treated her with high doses of prednisone to keep the kidneys functioning. She had all the bad side effects of the prednisone. So between the prednisone and the MM it was doing a number on her bones. In Oct of 08 she hurt her back. We found out a few months later it was compression fractures of three lower vertibrae. After a bone scan and 24 hour urine test with Bense Jones protein she was diagnose with MM at the end of Feb 09. Chemo was started with Velcade and Dex. She went to the hospital three times before they discovered she had a bad gall bladder and it was removed. She has had GI track problems for a long time and still can't figure that one out. Could be damage from the steroids. On the good side she has responded to the chemo. Her free light chain protein count is in the normal range and the pet scan from a couple of weeks ago didn't show any cancer. She has fractured three more vertibrae and is not very mobile. We use a wheel chair to go to the doctor. She has had a lot of pain and the pain medication causes side effects. Her blood counts are pretty good except for Albumin which is about 2.2. This indicates her general health is not too good. She has lost nearly one third of her body weight since Feb 09.

    I did call Emory in Atlanta a while ago to get a second opinion. They accepted to see us. However, due to her back pain and GI pain she doesn't want to travel at this time. We have switched to a different oncologist. We had difficulty communicating with the first one. She likes the one we are seeing now so that helps with her emotions. The back does seem to be getting a little better. If the GI issue would get a little better and she could eat more I think she could get into pretty good condition.

    Thanks for doing your blog. I have learned a lot from reading several blogs.

    I hope you get that cure you are after.


  2. Nice post Nick..way to get some facts/data out there on TT.

    I guess I am one of those patients who have decided to receive treatment elsewhere due to out of network costs, family constraints and not willing to relocate to Little Rock. I am part of the 85% low risk group that should respond well to TT and my recent numbers are proving that, although I am on a different protocal at U of M under the guidance and care of Dr. J.

    I am going through 4-6 cycles of R.V.D.D. which includes 2 weeks of Chemo (25 mg Rev: days 1-14, 20 mg of Dex: days: 1,2,4,5,8,9,11,12, Velcade days: 1, 4, 8, 11, Doxil day: 4) and 1 week off!

    I am on clinical study done in join effort with a lot of the leading institutions and funded by the hopefully this data makes it into good hands for longterm statistical analysis on its clinical effectiveness.

    The choice to stay local, maintain a work/life balance was key to my decision, not to mention the Cancer Center is 3 miles from my house. Plus, I feel that the RVDD approach which will conclude in a stem cell transplant and possible tandom is pretty close to Total Therapy in terms of throwing the kitchen sink at the disease. Although I know the Arkansas approach is much more than a lot of drugs, good care and some southern smiles. They definitely believe in what they are doing down there and there's no doubt that the hope they bring to patients is infectous.

    Quick question on numbers. Does Dr. BB release what the median age of his patients are down in Little Rock? I know I come from a unique perspective only being 29, but I can't think to believe that has to help the overall long-term survival rate. A lot of the patients I saw down in Little Rock seemed to be under the age of 50; whereas my Support Group in Ann Arbor I would say the median age is closer to 65.

  3. Phil -

    Good to hear from you! Yes, obviously picking up and moving to Arkansas for several months is not something that people can do trivially -- I was lucky that my employer afforded me the opportunity to take time off to focus singularly on my therapy!

    In answer to your question, I did some research and there are two figures I came across in various presentations BB has given: in one the median age is 60, in the other it is "nearly 65." He transplants all these people. So while you did bump into a fair number of young folks, there are plenty of older ones as well. I was in the transplant ward with someone nearly 90! He was the person that I commented looked like he had one foot in the grave when I first saw him -- and six weeks later he was walking around without assistance looking pretty darn good for his age, all things considered!

    Please keep me (us) posted on your progress -- you and your family remain in our thoughts and we want to help in any way we can!