A Northwest Lens On Myeloma: Putting “Risk” In Perspective
“Did your other doctor talk to you about your cytogenetics?” My current doctor, a myeloma specialist, asked me this while giving me a second opinion on my diagnosis.
It was the first time I’d ever heard the term cytogenetics. My doctor explained that I had a “del17” chromosomal abnormality, which made my disease “high risk” and potentially more aggressive than that of the majority of other multiple myeloma patients. Two years later, I understand this concept better, but occasionally my gut reverts back to that day and I become frightened that being high risk will prevent me from enjoying a longer, healthier remission.
Patients typically undergo a bone marrow biopsy as part of their initial diagnosis. Many labs will, in addition to standard diagnostic tests, perform fluorescence in situ hybridization (FISH) testing looking for any chromosomal abnormalities in the cancer cells. One such abnormality, del(17p), occurs when one of the "p" arms of chromosome 17 is missing. Patients with this abnormality, and others, are considered high-risk patients. While only a small number of patients are considered high risk, when you are one those patients it doesn’t matter how prevalent it is.
Being labeled high risk sounds scary, and in my research I often read that a finding of a del(17p) abnormality is associated with “poor prognosis.” Without understanding what this language really means, it was easy to believe my multiple myeloma was going to win the battle and my time remaining is shorter than most patients. That simply isn’t true.
High-risk multiple myeloma does not mean treatment failures are a certainty, nor is it a guarantee of shorter life. Being a high-risk patient may require extra diligence in evaluating treatment options, and may mean receiving more medication or even considering more experimentation to find a treatment that will keep the multiple myeloma at bay. It doesn’t, however, guarantee a negative outcome.
In terms I can understand, high risk means that I stand a better than average chance of relapsing sooner than most, and a better than average chance that my multiple myeloma will become resistant to treatment quicker than most. Like all statistics surrounding multiple myeloma, these are just statistics regarding how patients in this subcategory generally fair in relationship to patients without these abnormalities.
I found an interview with Dr. Ola Landgren in a 2012 Beacon article particularly helpful to put the concept of “high risk” multiple myeloma in context. Dr. Landgren suggests that if all multiple myeloma patients received limited treatment, everyone would be considered high risk. Their initial responses would be low, remissions would be short, and when relapse occurred, there would be no treatments left to battle the disease. On the other hand, if there were a cure for all forms of multiple myeloma, every patient would be low risk. Today, there are many effective treatments for the vast majority of myeloma patients, but not all patients respond the same. As he explains, “‘Risk’ is an interaction between biology and intervention. And intervention is a variable that changes between clinicians and institutions, and it is constantly changing over time.” So, high-risk myeloma is not inherently bad, it is just a type of myeloma for which research has yet to find a consistently effective treatment.
Multiple myeloma research and treatment is running at break neck speed. I received three cycles of Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone (Decadron) before I stopped responding. I immediately started Kyprolis (carfilzomib), Pomalyst (pomalidomide), and dex and saw a fast and deep response. Recent research indicates that both Kyprolis, and Pomalyst have benefits for del(17p) patients in comparison to Velcade and Revlimid. There is research of other treatments targeting high-risk patients. If future treatments prove effective for patients with abnormal chromosomes, we too might be considered standard risk in the near future.
Because I’m del(17p), my medical team and I decided to treat my multiple myeloma aggressively. We knew from the start that I would have an autologous stem cell transplant. While there is a reasonable debate whether a transplant is a necessary front-line treatment for standard-risk patients who respond well to initial treatments, it was not a debate for me. It is also my understanding that most myeloma specialists recommend up-front stem cell transplant for high-risk patients.
I will also follow an aggressive maintenance path. I’m receiving a lower dose of the same medications that I received in my effective induction treatment. I will likely stay on this program at least three years barring relapse or serious side effects. This plan means we will be more vigilant for symptoms of toxicity. I suspect I will always receive some type of maintenance.
Being high risk does not, however, change the way the disease acts in my body or how side effects of the treatments affect my body. I’ve been lucky on both accounts. We attacked the multiple myeloma before it did any serious damage anywhere, and I’m no more at risk of further bone damage or kidney failure, for instance, than any other multiple myeloma patient. So far treatment has been unremarkable, with good responses and mild side effects.
I’m approaching two years post diagnosis, over six months post transplant, and my doctors are happy with my progress and I’m feeling healthy. Nobody can predict how long my remission will last or what the future holds. “High-risk” or “standard-risk” predictions are just based on statistics, and those statistics don’t take into account my personal information, and they don’t predict how new treatments will behave in the future. Haven’t we all been told, “you are a statistic of one?”
Admittedly, the gremlin hiding in the back of my head occasionally reminds me that I’m a high-risk patient, and that some of the reports and statistics offering great hope to the majority of multiple myeloma patients may not apply to me. The gremlin tries to put a damper on my hope and get me to forget how good I feel and how lucky I am to still be able to spend quality time doing the things I like and being with the people I love.
When that happens, I lock the gremlin away and remind myself what it really means to be high risk.
In the end, I’m like all multiple myeloma patients. I trust my doctors and the rapid pace of the progress fighting this disease to keep me with my family for many, many more years.
───────────────── ♦ ─────────────────
Mark's Photo For The Month
My photo “Shells on the Shore” tells a more complete story when you know the context and understand the perspective of the photo. These empty clam shells are on the shore of the Tulalip Bay of Washington’s Puget Sound. They were likely placed there following a family feast, a tradition of the native Tulalip people for millennia, as their sustenance and culture revolves around the natural bounty of the water. The photo was taken by placing the camera low and into the shells themselves, altering the normal perspective of a person standing on the shore.
Photo copyright © 2013 Mark Pouley.
Mark Pouley is a multiple myeloma patient and columnist here at The Myeloma Beacon. His column is published once a month. You can view a list of his columns here.
If you are interested in writing a regular column for The Myeloma Beacon, please contact the Beacon team at .
Thank you for an upbeat approach to high risk and del(17p). I received my "high-risk" diagnosis in August 2015, responded well to Kyprolis, Revlimid, and dex (KRD), had a tandem transplant, and am now on maintenance. My maintenance is the same as before (KRD), and so far side effects are minimal. Like you I will probably always be on maintenance, but that isn't going to rule my life!
Thank you for column and for all your excellent writing, Mark. Your stem cell transplant story was one of my guides. You've already helped me so much - we are about the same age and similar timing in our story. I just wanted you to know I appreciate your writing and photography here.
Marvellous attitude Mark, I love it!!
Ian,
Multiple Myeloma Sept 2014
London, UK
Thank you Mark- my most recent bone marrow biopsy showed that I have developed del(17p), and I searched the medical literature to find that it "associated with significantly shorter overall survival and time to progression, even in patients treated with intensive chemotherapy." Your analysis was the upbeat message I needed to hear today. I was diagnosed in 2014 at age 54, much like you, and began treatment 14 months ago. Life is the journey, not the destination, and I remain hopeful with all of the new treatments in the pipeline. Good luck with your journey, and thanks for your photography and writing.
Mark - thanks for the high-risk info in your column. I am also del(17p) and high risk. I did 4 rounds of Revlimid, Velcade, and dex and then had an autologous stem cell transplant. I just celebrated my 2-year post-transplant anniversary. I am on Velcade maintenance. I enjoy your photographs - you have a great eye for the camera lens. Let's hope that someday soon a true breakthrough is found for all high-risk patients.
Nice job writing this column, Mark. You put high risk and multiple myeloma itself into the proper perspective. Best wishes on continuing your good response to treatments.
Thanks, Mark, for writing about a hard topic. I am higher risk because of del(13p) and translocation of 4:14. However, I am now 6 years post stem cell transplant. I have been through many lines of treatment, and yet I'm still here. I'm experiencing a new remission because of the Darzalex regimen. My understanding is that some of the newer drugs, which are in the category of immunotherapy, are just as effective no matter the cytogenetics. So we will just both keep putting that gremlin back in the bottle.
Thanks for writing this article. I was diagnosed with smoldering myeloma in 2014, and my bone marrow results revealed del(17p) and several trisomies. I hope that the trisomies offset the negative aspects of the del(17p). At least that is what I tell myself in order to stay positive!
It's nice to read about people with these high-risk factors still in remission or at least responding well to treatment.
Very informative article, Mark. Thank you. I really love your attitude about "high risk" and the wonderful description by Dr. Landgren. The recent advances in the treatment of multiple myeloma have given many of us lots of hope. My husband is also considered high risk because his chromosomal abnormality has never been seen at our medical center. Because of that and his condition at diagnosis, he has had aggressive treatments similar to yours. I am happy to report that he continues to be in complete response 18 months post transplant.
Dear Mark,
Excellent thinking in difficult times. I was diagnosed with multiple myeloma in 2012. Fortune favors the brave. Life is a journey. Gremlin is always in the back of my mind. Trust the doctors, they will try for cure. Already treatment has made a difference. We can make impossible things possible. I pray God to give you strength. Let us hope for the best.
Mark -
Thanks for addressing high-risk myeloma, and del 17p in particular. Our circumstances sound pretty similar, although my background as a cancer epidemiologist who mostly thinks about genetics meant that when I saw my cytogenetics report, I knew more or less exactly what it meant. The gene called TP53 (which makes a protein called p53) lives on the short (p) arm of chromosome 17, and it is frequently referred to as the "guardian of the genome." It has to be one of the few genes with a book devoted to it – not a bestseller, but I did see it on the shelves of our local chain bookstore. Many of the strategies for using drugs to kill cancer cells rely on getting p53 involved, and that's a problem for people like us who don't have enough of it.
I am 5 months out from tandem transplant, and have had a less deep (though still improving) response to treatment so far, taking Ninlaro-Revlimid-dexamethasone. As you say, we are all our own experiments.
Best of luck to everyone.
Rich K - Thank you so much for further enlightening me. I may have seen those numbers and ideas, but never explained so succinctly and simply so I made sense of it. That explanation helps a lot. You say that you have a "less deep response to treatment," and I will assume your labs still show a very small M-spike. I seem to have stabilized at 0.1 over months 5, 6, 7 post transplant. My biopsy at +81 days was very good showing nearly no abnormal plasma. It is your understanding it is our mutant TP53-less chromosomes the are hanging out?
Patty B - So glad your husband has reached a long complete response. May he stay on that track for many years.
Everyone - Thank you for the nice complements and encouragement. I wrote this column with myself 2 years ago in mind. Finding out I was high risk meant I needed to understand that. Everything I could find to read talked about the statistics. The shorter remissions, quicker relapses, faster resistance. Statistics don't help a patient, they only scare use. So here I tried to explain want it means to a single patient. How I deal with it and how it is the same as all multiple myeloma patients. We hope. We listen to doctors. We look to a future we know will continue to save us.
Mark,
Thank you very much for taking the time to help us understand.
Regards,
Chuck