Arnie’s Rebounding World: N Of 1
In statistics, N refers to the number of subjects in the sample, or the sample size. In a scientific study such as a clinical trial, N is the number of patients enrolled in each arm of the study. Generally speaking, the larger the N, the stronger the validity of the trial.
From a statistical standpoint, an N of 1 would have no real significance. In fact, we were always taught in medical school that an N of 1 is an anecdote, not necessarily worthy of consideration, and often dismissed.
In real life, however, when you are confronting cancer and you are the N, quite the opposite is true. The only thing that matters is the N of 1.
We are all familiar with clinical trial results. They all seem to sound pretty similar and are reported in a somewhat standardized fashion.
It goes something like this: 30 percent of patients achieved at least a partial response, average time to progression was x months, and ... I’m zoning out.
I want to get down to the gist of it, the important stuff: What do the results mean for me personally? Am I part of the 30 percent of patients who will respond, or the 70 percent who will not respond? At this point, it’s a crapshoot.
The reason it’s a crapshoot is that there are fundamental biological differences in the multiple myeloma of the patients who respond and those who don’t respond, and we don’t yet understand those differences.
This is the huge disconnect between the clinical trial world and the reality of a single patient.
A number of patients – hopefully enough to be statistically significant – are thrown together in a clinical trial. These patients may all be fundamentally different from each other; some will respond, some won’t. We are just not sophisticated enough yet to understand these differences.
This is the essence of genomics and personalized medicine. Everyone is an N of 1, but we are still using a crude, one-size-fits-all approach in current clinical trials.
At the stage that I am at in my multiple myeloma (having exhausted all standard therapies and being ineligible for almost all clinical trials), I have to embark on my own N of 1 experiment.
After months of waiting for approval and then completing seemingly mountains of paperwork, I have finally started a single-patient protocol of elotuzumab in combination with Revlimid (lenalidomide) and dexamethasone (Decadron) through a “compassionate use” program.
Since this is a single-patient protocol, we will hopefully have some flexibility – with the approval of the drug company and the U.S. Food and Drug Administration (FDA) – to modify and add other myeloma drugs as we go if the current combination doesn’t work.
Will it work? I have had more than one opinion telling me that it won’t. No one can say for sure. However, in this case, I’m not just a statistic. All that matters is me. I am more than happy to be an anecdote. It all comes down to that N of 1. So, of course, why not try?
However, I’m not putting all of my eggs into one basket. I am actively investigating and pursuing any and all options. Immunotherapy and genomics seem to be the hot areas that are currently generating all the buzz. They seem to be the promise of the future.
A great deal of work is being done to try to identify and characterize the genetic mutations that drive multiple myeloma. It is turning out to be a very complex and heterogeneous task. The goal is to identify which specific mutations are driving the disease in an individual and then use specific therapies to target these mutations – truly the N-of-1 approach.
Access to genetic profiling in multiple myeloma is becoming increasingly prevalent and available. I have had the testing done (my insurance even covered it) and obtained some potentially useful information, although it’s way too early to say for sure.
The problem is that what to do with the information is still very much in its infancy.
Work is also being done on “repurposing” existing drugs that have already been approved for other cancers for use in multiple myeloma. The most significant example of this effort is a group of drugs currently approved by the FDA to treat malignant melanoma. These drugs target genetic mutations that also have been found in certain multiple myeloma patients. Some multiple myeloma patients have already started using these drugs with some success.
Clinical trials of new drugs targeted to specific genetic mutations are being introduced or expanded to include multiple myeloma.
All of this is going to be exceedingly complex and will take time. It may even turn out to fall short of expectations.
The ultimate goal is for everyone to be an N of 1. After all, that’s the only N that matters.
Arnold Goodman is a multiple myeloma patient and columnist at The Myeloma Beacon. You can view a list of his columns here.
If you are interested in writing a regular column to be published by The Myeloma Beacon, please contact the Beacon team at .
Arnie: As always, thank you for sharing a crystal-clear picture of your uniquely sobering MM story with us. I am inspired by the grace and dignity that you exhibit as you meet the ongoing challenges. Having been enrolled in a large sample clinical trial, I still feel like a 'party of one'. I can only imagine how that feeling is compounded in your case. I join a legion of other folks who are pulling for you and praying for good results.
Keep up the good fight. Hope is a powerful thing.
Marvin
Arnie, this is the first time I have read your column and am surprised to learn that it is possible to conduct your own clinical trial. Unless I have the wrong end of the stick, this is what you are doing.
I have had MM for 18 years and, until the current trial of pomalidomide [Pomalyst, Imnovid] and dex came along, I had exhausted all of my options. If it is possible to conduct one's own trial, other possibilities open up for me and others like me.
How does one go about this? Did you enlist the help of your doctor? I live in Australia so obviously the rules will be somewhat different, but I am interested to know how going it alone is done, if indeed this is what is happening.
To have my doctor tell me that I have no options left is depressing to say the least. I am forever hopeful and positive, and my doctor's statement does not sit well with me. Surely there are numerous ways to approach treatment?
You give me hope. Thank you.
Hello Susan,
In certain very specific situations, the U.S. Food and Drug Administration permits access to experimental drugs on a case-by-case basis for an individual patient who otherwise does not qualify to participate in a relevant clinical trial. This is called "expanded access" or "compassionate use".
The U.S. program is described at this webpage from the FDA.
Arnie also described some of the rules and regulations related to compassionate use in this previous column of his.
Perhaps you could find out if similar opportunities exist in Australia and let us know here (and maybe also in the forum) what you find out.
Fascinating article, Arnie. Wondering why you are "ineligible for almost all clinical trials?" Is it the type/line of MM you have; too far along; insurance? Trials are all I have left also. Pomalyst / Velcade lasted 8 months, then daratumumab (3.5 months), now beginning carfilzomib (Kyprolis) / panobinostat.
A one-person clinical trial! You do well, you hear - you encourage us!
- Dave, 7.5 yrs and counting.
Arnie:
You are much more than an anecdote. Always have been, always will.
Fight on.
Thanks to the Beacon Staff for clarifying Susan's confusion. I want to be clear, I have been granted access to the drug elotuzumab, which is in active clinical trials. However, I am not eligible for any clinical trials and have run out of other options. The FDA has created a pathway for people in my situation called "compassionate use", or expanded or single-patient access. This allows the drug companies -- but does not compel them -- to release investigational drugs on a case-by-case basis for individual patient protocols.
Under compassionate use, the use of the drug and the program is monitored by the drug company and the FDA similar to a standard protocol. The links in the comment by the Myeloma Beacon staff explain this very well. I think that it is important that people understand that this pathway exists, but that it needs to be initiated by the physician, not the patient, and it is often a difficult and lengthy process.
To answer Dave's question, all clinical trials have a set list of inclusion and exclusion criteria. Some are pretty standard, but some vary from protocol to protocol. The two biggest exclusion criteria that I have are that I have had an allo (donor) transplant, and I nonsecretory disease.
Thanks everyone for your comments and wishes.
With my husband now at seven years fighting aggressive and refractive MM, close to the situation you are in, all I can say is stay with us, Arnie. You are a beacon.
Arnie, what a great column!
You've eloquently expressed something I've felt for awhile now. I'm participating in a large international clinical trial. But there's a more important (to me anyway) private little N of 1 biochemical experiment going on in my body.
Here's wishing you well in your N of 1 experiment.
Good luck with your individualized medicine ... I know you are in really good hands! It's good of you to share this with us here. It sounds like at least you did not have to wait without taking any drugs for a set period of time before starting on the elotuzumab. That seems to me to be a real drawback in starting clinical trials. I haven't been on one myself though, just have read about them. Best wishes, Arnie!
My N of 1 experiment worked. I am hoping yours does too.
With a disease as heterogeneous and complex as MM, I think that genetic testing should be mandatory. At least then we would know how many thousands of N = 1 exist.
All the best.
Hello Arnie, and Beacon friends! I just read your excellent column in a pub in Prague, where my wife and I are enjoying visiting our home town for a month. I congratulate you on a great explanation of your, and in many ways, all MM patient's challenge. All of us wish you success with elotuzumab, and other treatment. My situation resembles yours in many ways, having started a treatment regimen that is unique, after failing all other treatments.
My hope is that my side effects will remain quite manageable while in the Czech Republic, so I can enjoy fine food, beer, and many relatives and friends, possibly for the last time. To me, enjoying life to the max is one of the keys to successful treatment! Best wishes, Jan
Point well made: studies and statistics are great guides but in the end the only thing that matters is whether the treatment works for you.
Hello Arnie,
Right on my brother! You have described the angle toward treatment that is also right for me.
... and what Denise Hale said;
... and what R said.
Pumping my fist in enthusiasm for your article.
Thank you for your powerful message - we do all stand as 1s and you remind us of the strength we have as individuals and as a group. I am very hopeful that your treatment will provide you with excellent results.
Very helpful article, thank you.
Also, today's Washington Post front page has an N of 1 case story about a woman with refractory/progressing multiple myeloma, first treated about 10 years ago. And this time treated experimentally and so far successfully at Mayo Clinic with 100 billion units of measles virus.
I follow this because of my own situation, first treated in a clinical trial starting early in 2009. Last year, another round, including a stem cell transplant. I found your column when I googled on Stem cell transplant recovery," because I wanted to hear another patient's experience.
Thank you again.
Thank you for your comment, CherryW.
In case you are interested, you can find the Mayo press release about the virus study you mentioned here:
http://www.myelomabeacon.com/pr/2014/05/14/mayo-clinic-measles-virus-multiple-myeloma/
There's also some discussion in the Beacon's forum about the news:
http://www.myelomabeacon.com/forum/measles-virus-multiple-myeloma-t3287.html
When breaking news like this comes out, The Beacon generally includes the relevant press releases at its press release page,
http://www.myelomabeacon.com/pr/
and also let its readers know about the news via the Beacon's discussion forum and also through our social media pages (Facebook, Twitter, etc.).
Hi Arnie,
I really look forward to your columns. You don't feel sorry for yourself and you do the best you can do. I love the N=1 angle!. It perfectly encapsulates a lot of what we are all navigating.
"study says this, but what does that mean for me"? Keep up the good work and thanks for the great article.
I had the pleasure of dining with Arnie and his wife, Merle, last evening. I want to share how good and strong Arnie looks--showing steady improvement over our visits since his allo (donor) transplant. It is impossible to comprehend the time and effort that Arnie, Merle, his Moffit doctors, but especially renowned specialist, Dr. Ken Anderson, needed to slog and log in order to make his access to elotuzumab a reality. Every day Arnie lives is a gift; a gift for his family, friends and all of us in the myeloma community. He's a true trailblazer, using his N-1 philosophy to help break new ground that may help a number of us someday. I'm fortunate to call him my friend! And I expect him to be around for a while; a lot longer than his fellow doctors gave him close to two years ago.
Are you aware of a limited clinical trial at Mayo Clinic that used a mega dose of the measles vaccine? An article was just published in the USA Today about the trial. This may be the N for some myeloma patients. I know as a myeloma patient hope for a solution is something tangible that I can grab on to. Good luck and God speed.
Hi Paul,
Please see the comment we left just a couple of comments above, in response to CherryW's comment, with links related to the Mayo study you've mentioned.
Arnie,
Thanks for sharing your story with the rest of us in the MM community. I know this could be just another crap shoot, but let me suggest yet another: Did you discuss the option of a Rev/Dev/BT-062 trial? I am only at 2 cycles and seeing good initial response. Maybe you and/or someone else? I cannot say. Just a thought.
Best of Luck - Mike
Dear Dr. Goodman, when I read your column, I thought about the big gap between the scientific news on the one hand and the reality of myeloma (N=1) patients on the other hand. Dr. Anderson were just so extremely enthusiastic about the latest development in a recent video interview, that one could think, that myeloma will be curable soon. But: Most of us relapse and are afraid every bloodwork and MRI. So you made an extremely good metopher for the situation every patient has to deal with.
Although there might be new medications on the market, the entry to trials is a challenge, that some educated patients could manage. And time - we talk about seven years till it comes to 1st line treatment - is endless from a patient perspective. Could be a great item for patients organisations to pave better ways to new treatments without buerocracy. The internet could be the perfect tool for it. Not only the myeloma cell is our enemy, beurocracy is its supporter. You have to be quite educated, to research your possibilities. What's about older or not so well educted patients without a MD or PHD? Thank you for the important insights and good luck for you next step. Thomas (from Germany)
Arnie:
Todays announcement means you are not going to be lonely with your new treatment drug, elotuzumab.
Two things: Can we call it E-mab ? ...and are you always riding this close to "the Edge" of new treatments.?
Hope you have many more years, and a happy experience with this drug.
Regards,
Arnie, thank you for your column. You continue to inspire the myeloma community as you take your cancer cells to task! You have all of us out here: we're hoping and praying for good results and your complete return to good health.
Keep strong!
Tabitha
Sooo, Champ.
How goes it ?
Well, I hope.
Regards,
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