ME vs MM: Prognosis?
One of the first questions most of us probably ask after being diagnosed with multiple myeloma is "How long do I have?", or some derivative thereof. For me, I think the question came right after asking what multiple myeloma is, and whether it's curable.
Perhaps it might be better to take a more philosophical approach and respond by asking "How long does anyone have?", reflecting the fact that life is a crap shoot, stuff happens, and we truly don't know when we will die.
After all, barring any knowledge of the unforeseen, most people tend to get on with their lives and don't spend a lot of time pondering how long they have to live. Conversely, when you've been told you have a terminal disease, the future no longer seems quite so certain and it's not as easy to ignore the question.
For purposes of this column, I'm going to gloss over the more philosophical approach. I know I could get killed in an accident tomorrow, or I could have a heart attack on my next bike ride, or lightning might strike me, but those are all relatively random events with low probability and nobody has indicated they are about to happen to me.
I have however been told that I have incurable cancer, and given my nature, I'd like to have a better idea of what the future holds for me. I'd like to have an idea of how long I have to get things in order, how long I have to fill and empty my bucket list, and how much dreaming I should still do.
As might be expected though, I'm not really going to get an answer to this question, because there is no definitive answer to it. There are too many factors and too many unknowns governing the prognosis for multiple myeloma, not to mention new treatments being developed that offer better survival.
Having admitted this though, it still hasn't stopped me from trying to discern some kind of answer from the bits and pieces of data I've accumulated since being diagnosed. So get ready for some twisted logic
The first thing I struggled with is what my basic prognosis might be. Figuring that out is difficult because I'm in a clinical trial using a combination of Kyprolis (carfilzomib), Revlimid (lenalidomide), and dexamethasone (Decadron), commonly abbreviated as CRD, and there is insufficient data yet to determine the median progression free survival (PFS) or overall survival (OS).
Since Kyprolis is in the same class of drugs as Velcade (bortezomib), and since treatment using Revlimid, Velcade and dexamethasone (RVD) has been around a bit longer, I figured I could assume CRD would have similar results to RVD. However, data for RVD is also limited and the best I could come up with was a median PFS of 47 months, with median OS not yet determined.
So next I considered just Revlimid and dexamethasone (RD), figuring results for RVD and CRD would be at least as good. Based on data from ASCO 2012, the median OS is 88 months.
Therefore, lacking any better data, I'll just assume the median OS for CRD is also 88 months, recognizing that results should most likely be better than that.
Since 50 percent of patients fall below the median and 50 percent above, I next considered which half I was more likely in based on factors that contribute to better or worse response, and how much above or below the median I might be.
Based on an Italian study, patients reaching a complete response achieved better OS than those reaching a partial response or a very good partial response. I've reached a stringent complete response, but so have about 60 percent of the patients on CRD, so I guess I can't assume too much improvement over the median OS for that. However, I will be optimistic and assume I'm in the half above the median OS.
Based on a French study, the following factors all contribute to poorer prognosis:
- age greater than 55 years
- beta-2 microglobulin levels above 5.5 mg/L
- chromosome 13 and 17 deletions
- translocation from chromosome 4 to 14
The median OS for patients with two or more of these factors was less than the median OS for the entire group, while the median OS for patients with only one of the factors was 1.3 times greater than the median OS for the entire group. The median OS for patients with none of the factors had not been reached yet. I have none of these factors, so I should be able to assume at least a 1.3 improvement in OS, and most likely better.
I've also come across a few studies showing anywhere from a 1.4 to 1.7 improvement in OS for patients achieving a sustained molecular level response (also referred to as minimal residual disease).
So, since I have none of the factors listed in the French study, and since I have also achieved minimal residual disease, I expect that my OS should improve by a factor of 1.3 times 1.7, or approximately 2.2, to slightly better than 16 years.
Before everyone starts picking apart my calculations, I'll come clean and admit I threw this data together with no regard for sound mathematics. I did this purposely to illustrate how easy it is to get carried away and take data out of context, or use data in an invalid way, and produce garbage.
In my case, I truly believe the odds are in my favor to have better than average survival, but there's no way to determine how many months or years that may be. Furthermore, given the uncertainties and variety of factors involved, is it worth expending the time dwelling on it?
After almost two years with this disease, I'm gradually realizing that the philosophical approach is perhaps a better way to deal with it. There's no doubt I'll still think about my future, but instead of asking "How long do I have?", maybe it's better to ask "What can I do to get the most out of today?".
Peace, and live for a cure.
Kevin Jones is a multiple myeloma patient and columnist at The Myeloma Beacon.
If you are interested in writing a regular column for The Myeloma Beacon, please contact the Beacon team at .
Absolutely....take the philosophical approach. A trolley may hit any one of us tomorrow & the statistics won't mean a thing. There's so much unknown still with myeloma & its behavior that dwelling on an exact amount of time left to live is absurd. Why would anyone want to torture themselves with knowing the day they will pass away? Suzanne
I like your analytical approach..I use the same, delving into trisomes and gene aberrations. I believe genomics is where it's at..Good article.
As has been pointed out many times the median is meaningless.
Thanks for demonstrating why.
When I was diagnosed, my question was "what's the longest you know that a person has survived with this?" He said he know people that had lived over 20 years and so that is what I focused on. Not the 3-4 year survival that I found with Google back in 2005. The only thing I use statistics for is financial decisions and retirement planning. Otherwise it's mostly a matter of making sure I don't waste my time on stuff I don't want to waste my time on.
Hi Kevin, great column. I am in a similar CRD trial at the NIH for the newly diagnosed and I have often wondered about OS, etc. since our related trials are so novel and contain an experimental drug (carfilzomib....at least for the newly diagnosed) and there is no previous data. Thanks for breaking it down. I have met with or communicated with many MM survivors who are alive and doing well after more than 10 years. I feel I have many more years to go and that is how I will live my life. I also believe that an effective cure for MM is close at hand, whether it be a small molecule, immunotherapy, etc. That hope sustains me.
I think it is all about how aggressive your disease is at the beginning:
Where MM reflects chronic disease resulting from non-agressive or stable MM, I wonder if knocking it back with drugs may be like going back to an MGUS state, where survival for 10, 15 years or more is not unreasonable. In fact, I am not even sure it is necessary to achieve an sCR if one has such a disease profile. The initial MM may not even be fully malignant.
But where MM starts out as a highly agressive or poliferative cancer with high-risk genetics, I suspect that even a CR is no guarantee of long-term survival. In this case, the MM is already is a fully-blown, highly malignant state, giving rise to many subclones that will eventually rear their ugly heads.
In obsessing about survival, what is also irksome (as Kevin has pointed out in an earlier column)is the limitation of studies based on medians. What percent of patients live for 15 years or more? And what are their characteristics? This data simply appears to be missing in most studies and never tracked.
I've been in remission -- stringent complete response -- since June 2009. I had a stem cell transplant in Aug 2009. At my last bone marrow aspiration -- April -- there was no evidence of Multiple Myeloma. At the same time, I was mis-diagnosed for three years (I have non-secretory MM which means no M proteins in a blood test. The doctors ruled out MM early on based on that and I was treated for arthritis.) and as a consequence am in constant pain from six compression fractures and other skeletal problems.
So far I have had as good an outcome as possible with my treatment. But I know that it is very likely that one of these visits to the doctor will result in bad news. That is the reality.
I tell myself everyday that I am just as alive as anyone else on the planet who woke up this morning.
Hi Kevin, Thanks for your thought provoking article. It's great if one can get to the point of not worrying about one's sheer survival on a daily basis, since that is a cause of stress, and too much stress just isn't good for us! Of course, that can only come after the medical treatments have helped us out with taming down this awful disease, which does have similarly awful statistics to accompany the prognosis! The points you made about OS median survival not yet being reached with two of the newer drugs, the proteasomase inhibitors, is what gives me a lot of hope that the statistics lag quite far behind the realities of the current treatments. And when you read the 'news flashes' that come out frequently in the Beacon, it all seems pretty good for the future of myeloma medicine!
If we as patients try to take good care of ourselves, we should have a good chance for a long 'survival', right??
Kevin, my mom (aged 85) was told 3-5 years for her MM. Of course, she was not a candidate for a stem cell transplant. Most of the time she kept her condition and symptoms a secret from us. We shared many joyous, funny, interesting LONG phone calls with her. She didn't tell us that she had stopped her chemo because it made her feel so bad. Then she suddenly had a breathing emergency (no red blood cells with oxygen for the heart to use, of course). Citrus County Hospital was absolutely no help at all, was a waste of time for 3 days, and made it worse most likely, her oncologist Dr. Harer was no where to be found when we needed him, and she was sent to a hospice where she died 4 days later, surrounded by all of us. She died exactly 3 years, 36 months in fact, after diagnosis. She died in total peace and dignity with no discomfort or pain as far as we could tell. I have mixed feelings about it all, but I think she probably "did it her way", made her own decisions, maintained her independence right to the end, had time to get her affairs in order and tell her family and friends how much she loved them, was caught by surprise by her sudden turn for the worse, and did not suffer the inevitable debilitating effects of MM that might have happened had she lived longer. We miss her deeply every single day, but we are comforted by the fact that she let us know that she had lived a very full, enriching, interesting, fun life and that her death was a peaceful journey. She set the bar high--I hope to live and die that well!
Suzanne,
I think you hit it square on the head - if you let yourself get wound up in the numbers too much, all you end up doing is torturing yourself.
Ralph,
Too much engineering and math in my education, I can't help but look at things analytically, but I also realize I can't get too caught up in it. The genetic research also interests me, though I have difficulty understanding a lot of it.
Gary,
I've had discussions with other patients on PFS, OS, and similar statistics at various times and it's disturbing how much people read into this information without understanding how it can so easily be misinterpreted. My intent with this column and my previous column were to try and point this out a bit. Nice to hear you think I was at least somewhat successful.
Jan,
My first doctor told me 2-3 years. It took a bit of time to start learning my way around the MM minefield and being able to discern the current data from the out-of-date data. Unfortunately, I think this happens to a lot of people. It's nice when you start finding the 10, 12, 15 year (and longer) survival stories, the new treatments, etc. that provide hope.
Terry L,
While it can be frustrating not to have PFS and OS data for some of the newer treatments, the bright side is that means they're working well enough to not have reached the point to be able to determine those stats yet. Like you, I feel I have lots to do yet, and the CRD trial I've been on will hopefully contribute to helping do so.
Starter,
You make a good point. I've also considered a similar analogy that MGUS is like MM laying in wait, but it doesn't become active until it reaches some critical mass. Never looked into the data, but I wonder if the time to relapse after remission is similar to the time to progress from MGUS to active MM?
Matt,
Glad that you've reached sCR for the past three years. It's unfortunate you have non-secretory MM. I've only come across a couple others with it, and it took quite a while to diagnose their cases too. It's unfortunate, it seems to gives the disease more time to progress, whereas as some of the effects might be lessened or even avoided if treatment could start sooner. Hope your remission is sustained.
Nancy,
It's definitely easier to avoid thinking about our prognosis when we're responding to treatment. I still get a bit too caught up in the numbers though. Two cycles ago, my IgA took a bit of a jump up, and I found myself stressing about it until my next set of labs showed it was coming back down again. It's a catch-22 though, because if I wasn't monitoring my results, I'd end up being more stressed just because I didn't have any idea what was happening.
Barb,
I am so sorry to hear about your mother. Given her age, I can see why 3-5 years was probably a fairly accurate prognosis in her case. I'm glad she went in peace and with dignity. My father passed away this past March at age 89 due to complications from cancer and it was much the same. He did not want any treatment, just a chance to say his last good-byes to everyone, then went peacefully in his sleep. Like you with your mother, I hope I can be even half the person my father was.
Hi Kevin!
you wrote:
"Based on an Italian study, patients reaching a complete response achieved better OS than those reaching a partial response or a very good partial response. I’ve reached a stringent complete response, but so have about 60 percent of the patients on CRD"
Thank you for this!! I had no idea. One of the things I appreciate in life is how others bring new information to the table and your column did this for me. Now, I do have to admit I do have 2 or more of the factors than contribute to less than the median :(...howEVER...I have faith..that those too, will be altered by CRD!!
Thanks so much for an analysis that made me happier!
suzierose,
Glad I could provide some positive news. I too am hoping CRD will increase PFS and OS for those taking it.
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