Arnie’s Rebounding World: Medical Uncertainty
I have always been a huge believer in second opinions; however, one of the most stressful and anxiety-provoking things is when the experts do not agree. I am then in the position of having to sort through the differences, try to understand how they have arrived at different conclusions, and then try to make a decision based on available and usually inadequate information.
It’s not exactly news to anyone with multiple myeloma that there are a lot of medical decisions to be made during the course of treatment. It’s also understood that even from the time of initial diagnosis, in many situations, the answers are far from clear.
As I have progressed in my treatment and have gone down a road that seems to have fewer and fewer people on it, this problem seems to have become even worse. The questions have become more complicated, and the data to support any answer is much thinner.
I am now 11 months out from my donor (allogeneic) stem cell transplant. I relapsed with extramedullary disease (myeloma outside the blood and bone marrow) after the transplant but was able to get that under control with radiation and the “CYCLONE” regimen: Kyprolis (carfilzomib), cyclophosphamide (Cytoxan), thalidomide (Thalomid), and dexamethasone (Decadron).
I also had a donor lymphocyte infusion (DLI, an infusion of more donor cells) one month ago. The idea behind the DLI is to ramp up the new immune system even further to try to generate a larger graft-versus-tumor effect, in which the donor immune cells fight the multiple myeloma. The risk, of course, is to exacerbate graft-versus-host disease (GVHD) as well; GVHD is a common complication of donor stem cell transplants that occurs when the donor immune cells mistake the host’s cells as foreign and attack them. It is a delicate balancing act.
This is where it gets really tricky. The question now is how best to control the multiple myeloma, take advantage of the transplant and DLI to generate the graft-versus-tumor effect, and not be miserable or sick from GVHD.
The short answer is no one really knows the best answer.
There seems to be agreement on a few points. One is that I continue to have aggressive disease that requires continued treatment. The second is that single-drug therapy is probably not adequate. The third is that my best hope for some meaningful long-term survival is to be able to take advantage of the graft-versus-tumor effect of my new immune system. Beyond those points, everything else is less clear.
How soon after DLI should I start therapy? What drugs will best achieve the delicate balance of controlling the disease and taking advantage of the transplant without suppressing or over activating the new immune system too much?
As I have mentioned before, many of the myeloma drugs have an effect on the new immune system one way or the other. Velcade (bortezomib) and by inference Kyprolis have been shown to suppress GVHD. Thalidomide has also been shown to suppress GVHD. Paradoxically, Revlimid (lenalidomide), while a cousin of thalidomide, is known to ramp up GVHD. While Revlimid’s effect on the immune system can be used to an advantage to increase the graft-versus-tumor effect, there is significant risk of exacerbating serious GVHD. And it’s not know whether using Kyprolis will dampen the graft-versus-tumor effect.
There really aren’t enough people in my specific situation to have any meaningful studies to answer the questions about which treatments to use and when. Doctors are forced to rely on what is known of the basic science, anecdotal experience, and finally and sometimes most importantly, gut feelings.
I get all this. Of course I don’t want to do anything stupid, but at this point I am more than willing to take some chances and to try some things outside of the box. Somehow I don’t think that playing it safe is the answer right now.
We are planning with some trepidation to use Kyprolis starting two weeks after DLI and add Revlimid beginning four to six weeks after DLI. This might work, it might be a disaster. We can always change course in midstream if need be.
I know to some extent I’m a guinea pig. I accept that. I don’t think there is a lot of choice. The good news is that it seems like there are options.
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 .
"Somehow I don’t think that playing it safe is the answer right now."
It is scary to be an outlier. Words fail me, other than wishing you strength and hope for the road ahead.
Words fail me too Arnold. All I can say is that I wish the best for you and will be praying that the treatment plan in place right now will work. Thank you for sharing your journey. Many of us may find ourselves in your situation and will learn through your situation.
Dear Arnie,
Thank you so much for sharing. It is always interesting and worthwhile to read your columns.
I wish you the very best.
Lin
Very Best Wishes from Ian here is France, I will be following your progress, because we are all travelling on the same road. Bon Courage
thank you for describing what you are going through. You are a very courageous man entertaining a difficult situation to many unknowns. I am praying you will be guided and have peace and success in what you pursue.keep us all posted. ml
Hi Arnie, thanks for sharing your journey. I am a recent member of the MM club, and before Dec of last year I had never heard of Myeloma. I am sorry that you are going through such a tough road. You are going onto my prayer list and I never do that lightly, its not something I just tell everyone. I do understand what you say about having to make so many of your own decisions about your treatment, that's something that amazed me from the beginning. At times it gives me peace to know that what I am doing is of my own will but then I think that since I have only a few months of learning that I am the last person that should be making these decisions. Anyway, I didnt mean to get carried away. I do wish you the best and hope that your strength carries you through what you are going through. Thank you so much for sharing with us all and my prayers for you are starting today. Hang in there brother!!
My mother was just diagnosed with Multiple Myeloma, widespread disease. Her hip just broke out of thin air. Searching and came across this site and your post. All the best in the world to you on your novel treatments. Bless you for sharing your journey and thinking of helping others as you go.
Hi Arnie, I am sorry to hear of your current position with regards to treatment. I too was a guinea pig. I have also had an interesting time with GVHD. However I am in remission.
The problem with GVHD (you know this) is that the targeted organs are primarily unknown. We can say probably skin, liver and GI tract will be affected. Other organs are likely to be targeted but this will depend on the individual. My question to you is how much GVHD and for how long are you willing to put up with it to eradicate your myeloma? Are you prepared to maybe be on some sort of immunosuppressive treatment for the rest of your life? I guess it is either that or therapy.
If I had to do it all again I would still pick the same GVHD path with some modifications. It certainly wasn't easy. I would attempt to stimulate the donor immune system by some means, maybe by immunisation with a dead or partial vaccine (trying to mimic the adenovirus I caught ~3 weeks after my DLI). I would closely monitor ESR and liver function and any other test that measures inflammation. My acute liver GVHD was stage III/IV - they gave me IV prednisolone in the nick of time. BUT during the 2 weeks in hospital my paraprotein halved (it had never done that before)then halved again. My chronic GVHD of the fascia developed later (~5 months) when I was weaned off the pred. This was undiagnosed for ~4 months - the pain in my muscles would wake me at night.
It has taken just over a year for me to feel that my chronic GVHD is considerably less. My daily pred dose is decreasing. I have more freedom of movement, I have started a gym program under the guidance of an exercise physiologist - I can touch my toes again!
The best news I had last month - my myeloma specialist told me that my graft vs myeloma response was perfect. The inflammatory response and the decline in my paraprotein coincided beautifully. She doubted that the myeloma would come back. If it does I'll deal with it then. To top it off for the first time in years my liver and kidney functions were both in the normal range. So was the GVHD worth it - you betcha.
Whichever pathway you choose, I wish you all the very best.
Libby
Thank you for daring and being willing to be out on the edge, Arnie. It's "guinea pigs" like you that make it possible for those who follow to have a better chance... and I for one am very very grateful for those who were in your position the last 10-20 years... most of us reading this would be gone already if not for them.
Keep fighting... and know that many of us are behind you!
Hi Arnie,
It’s good to hear from you!
I also feel like I’m a guinea pig and as you say constantly trying to make THE BEST treatment decisions. I read so many studies but results are often conflicting.
I’m 10 months out from my allo. Didn’t reach CR, still immunofixation positive. I had three escalating DLI in February, April and May. In June serum lambda light chains were down to 32 (69 in February) so looking good. But in early July went up to 45. So last week I started Revlimid 5 mg and dex. Did get a slight rash after a few days but less now. Didn’t get much GVH from DLI just slightly sore gums after the third. I’m very aware of that GVH can put an end to my Revlimid treatment. Just have to keep my fingers crossed......I have neuropathy in my feet so I’d rather not try Velcade again. Pomalyst and Kyprolis are not available in Sweden. There is a study with daratumumab but I don’t think you are allowed if you have GVHD.
I wish you the best on your journey and thanks for sharing. Much appreciated!
Åsa
Arnie: You are very kind for sharing your sobering story and unique perspective with us. I am sorry to no end that the road you have traveled has been unbelievably difficult. Please know that there are many of us praying that your impending treatment plan is successful.
Thanks everyone for you support and comments. Great to hear from the other allo patients who are on a similar road. The key of course is to try to balance the antimyeloma effects of the drugs, graft vs tumor effect and Gvh effects . Not easy to dial that one in and different for everyone. Hoping that kyprolis/revlimid will walk that line. We'll see.
Hi Arnie..thanks so much for sharing your medical journey. Wishing you all the best and that you are improving after the recent treatments. This is such valuable 'social media'...the rest of us readers who have not had allo transplants are learning a lot about them also, even in the comment section here. Take good care of yourself and enjoy summer!
What a humbling experience, reading your article as well as Libby's response. It's true, we are all in this together, but some of us are more IN it! My prayers are also offered, Arnie — and for the cure!
Julia
Jan
It is indeed an art as well as a science. Sorry to hear about your recurrence. I am curious if allo has come up as an option for you. Your two suggestions are very good. I think the reason that they have not come up is that the focus post allo has been on using the drugs to manipulate the new immune system . Happy to talk
Thank you Arnie for your honest update almost a year after your allo transplant. Controversies at the cutting edge of MM (and other disease) treatment are intellectually stimulating and fascinating from the point of a clinician, but frustrating and concerning from the patient's point of view.
Being physicians is thus a blessing and a curse as we deal with this multivariant disease. No one's MM journey is identical, and the combination of factors to consider is unique to all of us, as you well know.
Switching from philosophical to practical management going forward, here are two factors to consider for you. The first is that knowing your Cereblon protein level may be useful, since a low level would indicate that any of the Imib´s (Revlimid or Pomalyst) are likely to be ineffective. Dr. Keith Stewart at Mayo Scottsdale can arrange it.
The second is a genomic analysis of your myeloma plasma cells since your allo transplant. In my case, I was surprised to discover a BRAF mutation on my original biopsy, which explains the high risk, recurrent nature of my MM. Only 3-4 % of MM pts. have it. Knowing that opens up a new therapeutic target, using FDA approved novel agents used for metastatic melanoma! Over 200 unique mutations have been discovered so far, and this individualized approach is the future of most of oncology treatment.
Now that all FDA approved meds for MM have failed to control my own recurrence a year after my auto transplant, either this, or trials using other monoclonal antibodies and other immunotherapies, are my best bet. The proper choice between these cutting edge options is indeed an art and a science!
My best wishes to you are added to all the others. May we all enjoy time with our families and friends, and live life to the fullest while science searches for a cure, which I believe is out there for a great majority of MM patients!
You are an incredible person. I have been following your story for the last 2 yrs when I was first diagnosed. I had a short remission & relapsed in April 2013 (less than 2yrs after initial diagnosis). Now I am going thru the Revlimid/Decadron stage preparing for 2nd autologous t/plant. I remember one of your articles stating that MM is now a full time job. I agree. I find this time around much more difficult. The Revlimid side effects have been horrible. I now wonder what will be the next step when t/plant number 2 fails which seems to be the case with MM. I have been very hesitant about the "allo" t/plant because of GVHD... but I will keep moving forward to fight this battle. I wish you all the best.
On behalf of the multiple myeloma patient community, I want to thank you for blazing a new, untested trail for those that are following close behind! Good luck, dear friend!
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