Arnie’s Rebounding World: Myeloma On The Edge
It’s been said over and over that multiple myeloma encompasses a wide spectrum of diseases.
It includes people with the precursor diseases monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. It also includes newly diagnosed patients with active myeloma, those approaching their first stem cell transplant, some patients who are fairly stable on maintenance therapy, and those progressing after various treatments.
I think the different phases of the disease are reflected well by the diverse perspectives of the contributors to The Myeloma Beacon. I, too, have written over the years about my experiences at various stages of the disease.
I am finding myself at a different stage now.
I have high-risk, relapsed, refractory disease that has progressed through treatment with all available standard therapies, including two autologous (own) stem cell transplants and an allogeneic (donor) transplant.
It’s multiple myeloma on the far end of the spectrum. I know I am not alone. There are many others like me. Having blown through transplants, chemotherapy, novel agents such as thalidomide (Thalomid), Revlimid (lenalidomide), and Velcade (bortezomib) and now Kyprolis (carfilzomib) and Pomalyst (pomalidomide, Imnovid) in all sorts of combinations, the disease marches on.
Like many others, I’m not ready to through in the towel. But where to turn to next?
We are inundated with the latest new drugs, advances, and “breakthoughs.” Many of the new drugs are only available through clinical trials, which have confining inclusion and exclusion criteria that have ruled me out.
Some of the new drugs are variations of drugs we have seen. We also hear of highly touted new therapies in the popular media, yet they are actually too far off to be of use now.
I have been on something of a fact-finding mission recently to try to sort all of this out.
Through research, emails, phone calls, and doctor visits, I’ve tried to explore myeloma on the edge.
I’m not trying to find pie-in-sky ideas and solutions that are far down the road. Instead, I'm searching for practical, immediately actionable solutions for my specific situation. I’m currently on an individual patient protocol with elotuzumab, Revlimid, cyclophosphamide (Cytoxan), and dexamethasone (Decadron) which, for now, doesn’t seem to be working.
Thus, I’m actively looking for my next option.
Here are the observations that I have made in my search.
First of all, while there is a lot of information and options out there, it is not always easy to sort through them in a meaningful, orderly way.
Second, even your own doctor may not have all the information or be in a position to evaluate all the options. Doctors have widely differing opinions, perspectives, and approaches in treating a disease.
I hate to say it, but not all doctors are equal. To be blunt, some are better than others. Some tend to be more conservative, waiting for evidence to accumulate before embarking on a certain therapy. That’s okay, but you have to recognize that approach. I, on the other hand, am looking for the thought leaders -- the progressive, out-of-the-box thinkers.
In the process of reviewing potential options, I was also reminded of some important points that I sometimes lose sight of.
One of them is to not to be too quick to start a new therapy. Try to get as much mileage as you can out of a treatment regimen before switching.
In addition, everything doesn’t have to be a home run. Even a treatment with which I can achieve stable disease for a few months has value for me at this point.
From the standpoint of specific treatments, while there is overlap, I found it helpful to break the available therapies into four basic categories: traditional chemotherapy, novel agents, immunotherapy, and genomics.
Traditional chemotherapy includes options such as VTD-PACE, DCEP, and others. The University of Arkansas uses a protocol of a slow continuous infusion of chemotherapy over a 30-day course.
Traditional chemotherapy has in many ways been a very successful therapy for me. At least for now, my disease still responds to it. I have been told by some that traditional chemotherapy is my best and only realistic route of treatment.
The problem is that the results are not long lasting. The only end game seems to be either slow deterioration of my disease or some bad complication.
Immunotherapy seems to be one of the hottest areas of research right now and might very well hold the most promise. Engineered T-cell trials being developed at places like the University of Pennsylvania, Ohio State, and the University of Maryland look like really exciting treatment options. Some of these options are available now through clinical trials.
Unfortunately for me, on drilling down, I found that immunotherapy protocols such as these – and most other ones – exclude allo transplant patients like me, at least for now. I nevertheless think that these trials might be excellent treatment options for some patients.
Genomics was a hot buzzword, but it seems as though enthusiasm for it has waned a little. Genomics involves testing a sample of a patient’s tumor for specific genetic mutations and then using a drug known to target that mutation to treat the patient. The problem is that this approach is turning out to be very complex, and there are not too many drugs immediately available now (except for some of the repurposed melanoma drugs), and the responses to the treatments seem to be pretty short lived.
All of this brings me back to the novel agents. There are literally dozens of novel agents out there in various stages of clinical trials.
So how do I narrow the choices? I have specific criteria I am looking for when choosing a drug.
I need drugs that have a different mechanism of action than the ones I have taken before. I could be wrong, but it is hard to get very excited about a third-generation proteasome inhibitor. I also need drugs that have good activity against my type of aggressive, fast-growing disease.
Finally, I need a drug that is available through either a clinical trial without randomization and without inclusion and exclusion criteria that would keep me out, or through compassionate use, single-patient protocols.
While all the details have not been worked out yet, the most promising drugs I have come across are a couple we have all heard about – the monoclonal antibodies daratumab and SAR650984 – and two we have not heard as much about yet, selinexor (KPT-330) and filanesib (ARRY-520).
I have always been as cautious and skeptical as anyone one about breakthroughs on the multiple myeloma front.
Perhaps it’s just wishful thinking on my part, but I am encouraged that it really feels like significant progress is being made. Options are available, but they are not always obvious and have to be actively sought.
Whether they will work is another matter.
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 .
Dear Dr. Goodman,
Best wishes with your ongoing search at the edge of the myeloma treatment frontier. Your words articulate all the hopes and fears of all of those going through this journey.
Sincerely,
Alex
Nicely written article, Arnie. I also feel greatly encouraged by the progress that's being made in myeloma drug development. I don't know how much I'll personally benefit from it all, but there is some comfort in knowing that this disease will become far less deadly at some point in the relatively near future.
Arnie,
I'm really sorry to hear that your current treatment does not seem to be working. But I'm glad that you have been digging and that it does appear that there are other options that might work for you.
Thanks for another informative and straightforward column.
I'm rooting hard for you!!
Mike
Hello Arnie! Myeloma on the Edge, now there's an appropriate description of what you and I are facing. You sure have a great way of expressing complex thoughts into organized morsels. Great job! Having just completed VD-PACE chemo over 5 days, I too am looking for better, non-cytotoxic options to suppress the MM.
At this point, I am most excited about the potential of CAR-T therapy, where one's own genetically modified T cells are attached to monoclonal antibodies to seek out all the malignant plasma cells, thus reawakening the immune system recognition that missed the initial mutation that started this disease process in the first place. This is a potentially curative therapy for some. I know previous allo transplants are an exclusion to the University of Pennsylvania trial, but University of Washington (Fred Hutchinson) is looking into trials with CAR-T as well.
Searching for new ideas for innovative therapy (or combinations) is a time consuming process, but well worth it. Hang in there; there are more answers out there! All the best, Jan.
Really nicely written. Like you, I had two auto's that only gave me 18 months remission, but then had to have a full allo. Unlike you, my allo has worked for many years, but I still wonder what my next treatment will be when/if I relapse. I was wondering when your article was going to get to monocloncal antibodies, because many MM experts agree that mAb's is the next near-term most favorable treatment area for myeloma. Wishing the best for you. -Jack
Arnie,
I appreciate you sharing the challenges you are facing with relapsed refractory disease and the research you are doing. I read everything you have to say. I am learning a great deal from your column that I am sure will help me and others who are in your same position or will be in the future. It must be frustrating and stressful to see so many new drugs in Phase 1 and Phase 2 trials and a fair number in Phase 3 that may have the potential to give you more chances if you can just hang on a little longer. I really wish that, for people in your situation, they would open up more compassionate use -- especially if supply is not constrained. I understand from a clinical trial perspective, with so many prior treatments, it makes it difficult to isolate the effectiveness of a new drug from other treatments or get meaningful results for newly diagnosed patients. But if you had a dramatic improvement, even as an individual, something could be learned from that.
Rock on, brother!
Thanks for your comments!
Jan, I hope you tolerated the VTD PACE well and that it works to knock the disease back down some. It seems like the CAR t cell route would be a really reasonable one for you. Keep me posted.
Jack, as you say, the monoclonals elotuzumab, daratumab and SAR are probably are among the most promising in the short term and most likely one of those will be the next approved drug for multiple myeloma.
Eric, you are exactly right, there are so many drugs in early trials and sorting through which ones are both useful in later stages and available through an eligible trial or through compassionate use is the biggest challenge. I agree there needs to be more accessibility to compassionate use for people with advance disease. The advice to stay alive until the next drug, that I have heard over and over again, seems to be more applicable than ever.
Hi Arnie,
Thank you for sharing your situation and putting it so concisely. It has helped me to organize my own thoughts and options.
You hit it head on when you said myeloma encompasses many diseases. I feel that I have a version that is not shared by most people (fortunately for them) and it feels frustrating at times. Kind of like, what am I doing wrong here?
I'm about 14 months from diagnosis and 9 months post auto transplant and have already gone through RVD, then Kyprolis, Pomalyst and dex and now Cytoxan, Doxil, Velcade and dex. Still doing radiation for plasmacytomas too! Some plasmacytomas have shrunk, some are more painful and perhaps progressing, and my M-spike seems to be inching up.
I think within my body there must be several versions of this disease.
Your categories of treatments are helpful to me for when I discuss the next options with my doctor.
Thank you for your thoughts and ideas and I'm wishing you all the best in your treatments.
Joy
The column is obviously informative regarding the options to be considered and for that I am grateful that you have shared your research. But for me it illustrates a larger point which I know is shared by many readers.
This disease is too variable and complex for us to simply leave it to our doctor's discretion to design a treatment strategy. Because there are so many options and because doctors vary so much in their approaches, a premium is placed on the patient's doing their own research, asking the right questions and making their own individual determination of the path to follow.
Aloha Arnie,
Thank you for sharing your research with us. You are indeed on the edge and ahead of most of us in "line" behind you. Your continuing successes and failures represent a trial of sorts to the rest of us. Figuring out what will work for you and how you can get it is going to be the same dilemma we all face at some point.
Continuing to share your story with our community is doing more good than you can possibly imagine. Keep up the good work as long as you are able!
Aloha
Tom
Mr. Goodman, I have been a regular follower of your column for a few years now and I have learned an enormous amount from you over that period of time. Our situations are very similar, but my disease progression has trailed yours. Your sharing of your experiences has helped me through some difficult decisions.
I am currently at a very critical crossroad of my treatment. If you don’t mind I’d like to request your feedback.
I have high-risk, relapsed, refractory disease that has progressed through treatment with many (Revlimid, Velcade, Kyprolis, Pomalyst, Decadron) available standard therapies, including one autologous stem cell transplant.
I feel like I’m on the far end of the spectrum because drugs like Cytoxan and daratumumab have had no or little effect for me. I’ve seen them work wonderfully for others. I’ve been blessed to get onto some of the trials that I have, but my disease seems to be getting smarter and smarter at figuring out ways around these drugs.
I looked into the engineered T-cell work being done at the University of Maryland but I do not qualify because I do not have an HLA type of 0201.
The disease was starting to run out of control, so I recently went through cycle 1 of a presumed 2 cycle DCEP regimen. I’m anticipating good results, but I’m concerned about what’s next.
I have doctors and I have family members that fall along the categories of “conservative” or aggressive (the thought leaders — the progressive, out-of-the-box thinkers). The conservatives want me to stay the course and work through more drugs and/or combinations of drugs. The aggressives think that an allogeneic transplant is the best next step. I have multiple 9 out of 10 match donors.
Assuming that I can get my disease back into remission, I’m considering one of the depleted t-cell, allogeneic transplants being done out of Sloan-Kettering.
If you were me, would you be considering an allo (given all that you know, risks of GVHD, trial exclusion, etc.) at this time? Or would you be considering a second autologous or more chemo cocktail experimentation?
I own my own decision but I’m interested in your thoughts. Thank you!!!
Hi Dr. Arnie,
You're such a champ! I admire your strength, and your ability to cancel out the "noise" and focus on the most important components of your treatment. Your perseverance and clarity of thought are great advantages as you fight this disease, and I imagine that they're just a few in your mighty arsenal. Here's to finding a new and improved treatment solution, and know that you have a whole lot of us rooting for you.
Keep your chin up!
Tabitha
Hi Arnie
I am a Brit living in South Florida with myeloma too and have been following your column for a while now. Being from the UK, I often check out European websites for myeloma updates. I remember coming across a study that was done at the Karolinska University using a drug called sorafenib. Maybe something you could research.
Good luck and positive thoughts for you and your family.
Hi Michelle,
Thanks for your comment and for mentioning research related to Nexavar (sorafenib).
There was a press release put out about Nexavar as a potential myeloma therapy about two years ago. And, as you correctly remembered, it involved some research done in Sweden. One of the Beacon's readers posted the press release in the Beacon's forum here:
"Nexavar (sorafenib) - lab vs. trial results"
However, as the reader also pointed out, the Swedish study was a lab study. More importantly, there has been a Phase 2 trial that tested Nexavar as a potential myeloma therapy, but it was halted because the drug did not show sufficient efficacy. Here is the Beacon's news story about the development:
Nexavar Shows No Effect In Phase 2 Study (ASCO 2009)
That said, there also was another lab study conducted by German researchers that found that Nexavar has anti-myeloma activity. It is mentioned in this set of Beacon Newsflashes:
Beacon NewsFlashes – February 25, 2013
Despite the promise Nexavar has shown in the lab as a potential myeloma therapy, the results of the Phase 2 study seem to have deterred further development of the drug as a myeloma treatment. There are not currently any ongoing trials that we are aware of testing the drug as a myeloma therapy.
Here in the U.S., it still might be possible in some situations for a physician to prescribe Nexavar to treat a myeloma patient, since the drug is on the market as a treatment for liver and kidney cancer. This would be off label use, however, and there might be issues with getting insurance coverage for such use of the drug -- particularly given the results of the Phase 2 trial we mentioned earlier.
Arnie,
Thank you for sharing your research. As a recently new myeloma patient, two years out, I learned a great deal from your post. Stay strong and fight hard!
Sue
Hello Arnie,
My husband was in the phase 1 trial of KPT 330 [selinexor] starting June 2013. He had been diagnosed with multiple myeloma 13 years previously and gone through all the standard treatments. His disease was tracked by light chains and his Kappa counts were over 20,000 when he started the trial. KPT 330 gave us another year together which we valued.
Said it before and I'll say it again ... you are a TRUE inspiration, doctor!
Coincidentally, I just learned of KPT 330,
http://karyopharm.com/products/products-kpt-330/
And here's a link to information about the related clinical trial:
http://clinicaltrials.gov/show/NCT01607892
Thank you for all of your invaluable contributions to your fellow journeymen and women!
Steve
Thanks, Patricia and Steve, for posting about KTP-330 (Selinexor).
You can find some additional information about Selinexor and its recent clinical trial results in this forum posting we made right after the trial results were announced about a month ago:
"Selinexor + dexamethasone - initial trial results"
The posting includes a link to a related press release here at The Beacon as well as several relevant conference abstracts.
Hi Arnie, I hope it is not 'wishful thinking' at all on your part for you to find a therapy that is long lasting in its effects. I don't quite understand the rationale of the science behind your sentences...
'I found that immunotherapy protocols such as these – and most other ones – exclude allo transplant patients like me, at least for now. I nevertheless think that these trials might be excellent treatment options for some patients.'
Thanks for suggesting all the books on the list for the book club. Perhaps we should start posting about them soon? I know one person already commented on 'The Emperor of All Maladies', which you suggested. Jan Stafl has also indicated that he would post some comments about 'Enjoy Every Sandwich'!
Again thanks everyone for the great comments.
Jim, to answer your question directly, yes I personally would could consider an allo transplant. I was faced with the same decision 2 years ago and chose to go in the that direction. Of course everyone is different and there is no right and wrong decision. I always tell people there are two things to consider with an allo. One is: Will you survive the transplant and not wind up with debilitating GVHD? And two is: Will it work to control the disease? For me, the answer to the first was yes and no to the second. But it did give me something of a reset with the drugs and I am alive two years later. I have not regretted the decision for a second. My only concern would be I'd feel better if you had a 10/10 match.
Thanks for the info on Selinexor, Patricia. Glad to hear of your success with it. That is definitely one of the drugs I am focusing on right now and am pretty up on trials out there.
Nancy, to clarify what I was trying to say is that the CAR-T cell trials, as they are currently written (at least for now), exclude allo patients -- mainly to avoid adding another variable to the research. But for those who have not had an allo, I think they offer a very good option. Also great work on getting the book club going -- very cool idea.
Arnie,
Pat K might have mentioned bendamustine (Treanda) to you. Berenson has me on it and it's been pretty successful. Doxil and thalidomide did nothing for me.
Matt
Arnie,
While you might have heard of these, here is a list of seven (7) emerging treatments that you did not mention in your post:
(1) Panobinostat - a Histone Deacetylase Inhibitor; the same class as, but perhaps not as effective as ACY-1215 (which you did mention).
(2) Genetically engineered measles virus. Research published in Mayo Clinic Proceedings, May 2014.
(3) N-methyl-2-pyrroldione (NMP)- NMP is a solvent that can stimulate the immune system and kill MM cells. Research at The Peter MacCallum Cancer Center, reported in Cell Reports, April 2014.
(4) The use of genetic engineering to equip T cells with a Chimeric Antigen Receptors (CAR) to target CS1, expressed in MM cells. Reported in Clinical Cancer Research; Research at Ohio State University, March 2014.
(5) Use two-drug regimen of Chk1 and MEK1/2 inhibitors to circumvent Mcl-1 up-regulation and ensuing resistance to proteasome inhibitors. Published in PLOS ONE, March 2014.
(6) VLX1570 –USP14/UCHL5 inhibitor. A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Dana-Farber Cancer Institute Researchers reported in Blood. January 2014.
(7) Engineered T Cells with affinity enhanced TCR. “Engineered T-Cells Expressing An HLA-Restricted Affinity-Enhanced TCR in Advanced Multiple Myeloma Patients Post Auto-SCT Engraft and Are Associated with Encouraging Post Auto-SCT Responses.” Teams from University of Maryland, University of Pennsylvania, et. al. presented at ASH 2013 Annual Meeting. December 2013.
Additionally, there are some interesting research findings that involve the use of "nano-technology" applied to treating MM.
I wish you the best,
Mark
P.S. I am newly diagnosed as of 7 April 2014. Induction therapy went very well and I will forgo the ASCT route for now and opt for maintenance until relapse.
Arnie,
In my previous post, I forgot to mention Kinesin Spindle Protein inhibitors such as filanesib (ARRY-520).
Mark
Mark, thanks so much for your list. I am always interested in as much information as possible. I actually did specifically mention a couple from your list in my article, including the CAR t cell studies and ARRAY 520 (filanesib), which is the KSP inhibitor.
But more importantly, your list points out the larger point that I was trying to make. There is a disconnect between the therapies that we are tantalized with in the popular press and even some of what is presented at meetings, and what is immediately available, accessible, and – most importantly – applicable and likely to be helpful to a given situation. I am interested in therapies that meet those criteria now.
That is what is difficult to sort through. There are many promising therapies out there. But as you mention, some of them are not even in clinical trials yet. It often takes 6 months to a year to launch a clinical trial. In this article, I was trying to focus are things that would be helpful to me and hopefully others in my situation right now.
Arnie,
Your knowledge will be used by many for years. When I get to the next stage of treatment, I will review your columns and use that information to make better decisions. Thank you so much. Stann
Dear Arnie,
My sister thinks I have this. My last extensive blood tests were 13 months ago and all were normal. Can it sneak up on a person all of a sudden?
I was told I had fibromyalgia about 10 years ago so all my aches and pains have been dismissed as that. I'm 53 and getting more and more symptoms of MM but haven't asked my doctor to check. I feel pain in my bones but people roll their eyes and say you can't feel your bones. It's pinched spinal nerves (and/or I'm a hypochondriac.) I also have been having a great deal of purpura on my forearms without injury. Sadly (ha!) I have not lost weight.
Lately they have been checking my kidneys to find out why I have constant UTIs. Somehow MM came up and it's driving my sister crazy. She thinks all of it fits me.
If I was fine a year ago is it possible to have acquired this so quickly? Should I be a crazy lady and ask my doctor to check for this, along with MS...anything to explain my recent rapid decline. Doctors don't like it when you try to tell them how to do their jobs. I've been 'fired' from a primary care physician once before for asking too many questions.
Thanks in advance,
Janet
Best column ever, good friend! Real, insightful; you are helping so many in a number of different ways. Rise up, myeloma community! Show your appreciation of Arnie--a true myeloma hero!
Hi Dr Arnie
You might want to take a look here [Patrys press release about results for single patient treated with PAT-SM6].
They made special consideration for a MM patient to try their drug. All the best in fighting, and great article.
Dear Arnie,
Thank you so much for spending the time to write down just part of what you and your family have been experiencing with this battle fighting multiple myeloma. I am sorry to hear that your allogeneic transplant has not gone as planned. I hope by God's grace there will be a better solution for you to finally kill this relentless disease.
Our path seems very similar to yours on the surface. I have had two autologus and one allogenic bone marrow transplant over the years. In my case, I thank God that I have not experienced any GVHD whatsoever! Unfortunately, the donor's T-cells have not been able to replace my T-cells, so we did not get the graft vs. tumor effect as desired. The donor T-cell count is measured every three months and is in the low teen percentage number. MM has come back and I went back to the Velcade / Decadron chemotherapy treatment for several rounds.
Unlike before, either because of the donor or because of God's grace, my blood counts remain totally normal for the many months of Velcade / Decadron treatment. And the kappa light chain cancer number went down to just above normal, which is good news. However, the side effects of neuropathy in my feet and legs got really bad. I also struggled with the Decadron's side effects of little sleep and a changed argumentive personality.
We needed a break this summer, so I asked my oncologist to stop the treatment for now, which she agreed to do. My recent kappa light chain blood test showed a spike of doubling from the just above normal number. We know this means the MM as usual for me continues to not stop! We anticipate that my oncologist will start me on carfilzomib [Kyprolis] when the kappa light chain cancer number gets too high. In the meantime, we are hoping to enjoy ourselves and travel back to Europe in the near future before any treatment starts back up again.
May God be with you and also with all the people who have shared on this blog. Best regards, David