Arnie’s Rebounding World: Multiple Myeloma On The Ropes - Really?
As an avid follower of Google alerts for multiple myeloma and a reader of all things multiple myeloma on the Internet, a recent article caught my attention.
“Novel Therapies Put Multiple Myeloma on the Ropes” read the headline from the Oncology Report Digital Network.
The article led off with the statement “A sweep of new agents are poised to deliver what could be a knockout blow to multiple myeloma."
It then quoted Dr. Jeffrey Wolf, the director of the multiple myeloma program at the University of California, San Francisco, saying "We have made such tremendous headway in myeloma, except for those exceptional cases with ... adverse prognostic features."
"As a disease," Dr. Wolf added, "[multiple myeloma] seems to be on the ropes.”
Hum, really? After seeing this article, I knew I wanted to write about this as it related to my own experience and situation, but it has taken a little while to get my mind around it.
The article goes on to describe some of the new novel agents in the pipeline, many of which we have been hearing about and were reported on by The Myeloma Beacon from the recent American Society of Hematology annual meeting. Carfilzomib (Kyprolis), the new proteasome inhibitor cousin to Velcade (bortezomib); pomalidomide, the third generation of thalidomide (Thalomid) and Revlimid (lenalidomide); the histone deacetylase inhibitors Zolinza (vorinostat) and panobinostat; the monoclonal antibody elotuzumab; and others were all mentioned.
Don’t get me wrong, this is all exciting stuff and it’s great to see the amount of work being done.
But let’s be clear. In reading the results carefully, most of these developments seem to represent incremental changes at best. I’m just not sure we are at the point of “on the ropes.”
I do think some clearer distinctions need to be made.
First of all, there is no question that the outlook for multiple myeloma patients has improved greatly over the last 10 years. The use of novel agents has helped double survival during that period.
It seems the picture is especially good for patients who are diagnosed now. Multiple drug combinations of novel agents, stem cell transplants, the trend towards pushing for better complete responses even after transplant and maintenance therapy do truly seem to be changing the landscape. When and if these patients relapse, the drugs will only be better.
But what about patients who are further along in the treatment? People who have been treated with Velcade, thalidomide, and Revlimid and who are relapsing now?
The path is far from clear. That is my situation now.
It has been almost six years since my diagnosis. At various times during the course of treatment for multiple relapses, I have been on Revlimid, thalidomide, Velcade, and several combinations of these. I have tried pomalidomide in a clinical trial.
All of these drugs worked for a period of time and have allowed me good quality of life during that time.
One year ago, after a bad relapse, I underwent a salvage second stem cell transplant, which I had written about in an earlier post.
Initially, the results were very good. However, after about 10 months on maintenance therapy with thalidomide and Velcade following the transplant, my M spike started going up again and I am now back in full relapse mode.
So now what? As I said, the path becomes much muddier.
As I and others have said before, there are no right or wrong answers; however, I am not even sure there are any good answers.
Certainly, all the investigational drugs mentioned are available through clinical trials. But even that is not that simple.
First of all, certain clinical trials are available only through certain treatment centers. I am, of course, more than willing to go anywhere if it would help.
Secondly, many clinical trials involve randomization. That means that even if you do travel for the clinical trial, you may wind up being randomized to the ‘standard of care’ arm of the trial and not receive the new drug, at least not initially. Definitely not an option in my situation.
Most importantly, in heavily treated, Velcade- and Revlimid-refractory patients, most of these drugs seem to only be effective in about 20 percent to 30 percent of patients at best. Additionally, the responses are not necessarily very long.
Carfilzomib, for example, which is available through an expanded access program called C-MAP until FDA approval, is only effective in about 20 percent of Velcade-refractory patients. Better than nothing, but I sure would be hoping for better odds than that.
Furthermore, under the C-MAP program, carfilzomib cannot be combined with any other drugs except dexamethasone (Decadron). There are some carfilzomib trials combining it with other drugs, but which one is no better than a roll of the dice.
As another example, Zolinza plus Velcade in Velcade-refractory patients worked in 11 percent of the patients. Not very impressive.
I have what I feel are two of the best myeloma specialists in the country, Dr. Melissa Alsina at the Moffitt Cancer Center and Dr. Ken Anderson at the Dana-Farber Cancer Center, and they do not even seem to be sold on the next great idea.
After some discussion between them, the decision was to put me on a combination of the old drug cyclophosphamide (Cytoxan), which is being revived in multiple myeloma; Velcade; and dexamethasone, abbreviated as CyBorD.
The decision was based on the need to do something quickly because of the rapid rise in my M spike and the fact that I had taken cyclophosphamide before my salvage stem cell transplant last year with a good response.
Unfortunately, this regimen was of no help.
So that’s where we are right now. The next step is inpatient chemotherapy again.
Right now, I’m feeling more like multiple myeloma has me on the ropes than the other way around.
Arnold Goodman is a multiple myeloma patient and columnist at The Myeloma Beacon.
If you are interested in writing a regular column to be published by The Myeloma Beacon, please contact the Beacon team at .
Hi Dr. Goodman, I enjoy reading your very informative columns. Have you given any thought to trying to get enrolled in a gene therapy/vaccine trial like those at UPenn? I am monitored at UPenn and my doctor, Edward Stadtmauer, told me that there are two cutting edge ongoing trials. One involves introducing genetically altered cells back into the patient like the successful CLL trial at UPenn last year. The other involves a vaccine. Thanks again for your columns and good luck!
These are the two trials Terry is referring to:
http://clinicaltrials.gov/show/NCT01245673
http://clinicaltrials.gov/show/NCT01352286
The gene therapy techniques being tested in these trials are said to be similar to the one discussed in this Beacon article:
http://www.myelomabeacon.com/news/2011/08/12/gene-therapy-advance-in-leukemia-suggests-new-treatment-options-for-multiple-myeloma/
Hang in there. I am right with you. Did transplant Feb, 25,2011 and did get CR but already might number is moving up fax, tried Velcade, rev , dex and still moving up, going on the CyBord starting Thursday, hoping to get some control of the disease. Here the vaccines are helpful once the number is low and cancer in control but not while we are in active/progressive stage.
Dear Arnie,
I am sorry to read that you are in a difficult place. Dr. Wolf was the multiple myeloma specialist that I went to for a second spinion. I thlink he is wonderful and he is very forthcoming. If you cannot visit him in San Francisco, I think he would reply to you if you sent him an email. I realize that you have excellent specialists already, but you might want to give it a try.
The very best to you.
Linda
Yeah... no illusions here as regards my understanding of the literature. There is certainly a lot of positive research activity regarding MM, but "on the ropes" would very definitely be an over-statement at this time, I think.
Mind, as a newly diagnosed individual (last January) who has gone the radiation/chemo/ASCT route with good results to-date, I do have a certain level of optimism... but that optimism is to the degree that I hope, pray, and to some degree believe that I have a real shot at another 8-10 years of life ahead of me. Good news indeed, but clearly not a cure scenario.
Dear Dr. Goodman, Have learned a lot from your clear, insightful columns. Am wishing you all the very best on your new treatments, and will pray for a positive turn of events for you. I agree that the expression 'On the Ropes' will perhaps be true for some patients, but not for all. Each person has a unique reaction to their treatments, and one cannot generalize that broadly.
I agree (and relate!) with you 100% Arnie! I was a bit "underwhelmed" by a lot of the data while I was in San Diego at ASH last month.
Glad you are speaking out about how you feel. "Ditto" from me! Hang in there- Pat
Hi Arnie,
Yep, I read that same headline from google alert last week and had the same thoughts you've expressed above...I just chalked the headline up to it likely being a misquote by the reporter...perhaps I'm being too generous?
All the best,
Steve
I too agree. While I fully understand the excitement for those researchers and treating physicians in the world of MM, who have been at it a long long time, we are not there yet. In Arkansas, Barlogie has been focused on the High Risk, ultra High Risk group and garnering others to get on the band wagon to put time and energies studying this group, as he believes it is this group we will all end up in sooner or later and this group that holds the key to the answers we need.
Holding the relapse at bay as long as possible, sustained CR, has made great strides - good news. But for those where who are relapsing, repeatedly, now, the answers don't seem to be presenting themselves yet.
Thanks everyone for your comments. It seems most everyone is on the same page with this one. Unfortunately the history of cancer research and treatment often offers promises of cure well ahead of reality. Thanks for the vaccine advice but I looked at those trials at Penn and it does not look like they would apply to my situation. You have to be transplant eligible and have stored stem cells that can be altered. Again this is part of my point is that not all trial, as great as they may sound, apply to all situations. As Robin noted the key for right now for me is to get the numbers to stop going up quickly and to stabilize things with the chemo then figure out what regimen might be next. Hopefully will now more by next month
Dr. Goodman, sorry to hear of your difficulties ; they say that we all eventually will try everything available. However you don't mention your test results such as your FLC results. The Binding Site ( the company that manufactures the Freelite test ) in retrospective studies found that up to 10% of relapses were as a new clone making light chains only. When I relapsed 3 years ago for the third time it was as this Light Chain Escape as a new light chain only (LCO) kappa . My original IgA kappa also became active. In essence I had 2 active types of myeloma and each one required a different treatment as revlimid 25mg/dex 40mg didn't touch the LCO disease and it required the addition of velcade. I would assume that your oncolgists have looked at this. As to which drugs to try, you are right that it can be a mystery. Revlimid and velcade alone were nothing great in my opinion but together acted synergistically. Carfilzomib with pomalidomide and dex may work synergistically as well ? Elotuzimab certainly gives a different approach if added. ASH reported revlimid and it together gave improved results. If your FLC are from your original clone then their response is supposed to be rapid as their half life is 3hours as I'm sure you know, so a great deal of time won't be wasted determining if benefit exists. Good Luck, you are certainly in the hands of top oncologists.
Thank you for your info: In fact thats exactly my conclusion when I read the article about " Multiple Myeloma on the ropes".
Please see this link http://impreso.milenio.com/node/9086660
I was very impressed when I saw it. Its seems to be disrupting treatment.Good luck and I think its woth to fight, something like the new treatment, this article describes, will come.
Best,
Hi Arnie,
I saw the same headline (and had it forwarded to me by others). I am trying to live a normal life with Multiple Myeloma, but planning for the future is agonizing. I had a good response to Stem cell transplant, however pressure is on to get as much accomplished as I can in the next short while that I am medication free. My doctor reminds us Myelma is not like Lymphoma where at three years you can say your are potentially "cured". At three years you can say, I had a "good response to stem cell transplant", but are constantly watching waiting for relapse. So in essence, on the ropes would mean we are on the offensive, when in reality we are still holding up our gloves to protect our faces deffensive
I too agree but am even more cynical: I recalled when I read that article -- and I just confirmed -- that Dr. Wolf is not exactly an unbiased commentator. Indeed, here in the disclaimer at the end of the article:
"Dr. Wolf disclosed that he is on the speakers bureaus of Millenium, Celgene, and Ortho-Biotech, and is a consultant to and speaker for Onyx."
I regard his comments as essentially a pitch for long-term, multi-agent therapy. The more the better.
I also find myself wondering whether drugs such as Velcade or Revlimid would ever be approved if the indication was something other than a deadly cancer that has no cure.
I hear what you are saying. This cancer drugs that are daily "pills" are very very expensive, and since they are not administered in the hospital the patient is the one who needs to find funding, or pay out of pocket thousands of dollars. We are happy to be have these treatments but they are no walk in the park.
Hey Isabel
No habla espanol!!
Alyssa, I do like the boxing analogies. Dan, I am not personally as much of a cynic of drug company motives. But i know that many people are, and I do understand competely where they are coming from. I do agree that at times physician/scientists who are serving as speakers and on the advisory boards of these companies are very much acting as "cheerleaders" for the drugs being touted, and that conflicts of interest clearly arise. At this point I have no problem with expensive daily pills if they would work!
I actually work for a drug company - so am not cynical per se. My concern -- I do not need treatment yet but may soon (who knows) -- is that these current drugs are riddled with toxic effects that seem to sideline the vast majority of patients who post on this site. Frankly, treatment scares me outright. I have seen too many stories of people going into early retirement or quitting their jobs outright.
I would like to hear more comments from those ascribing to the low toxicity/high-quality approach of Mayo Clinic: revlimid plus low-dose dexamethsone. I would much prefer steady control of disease with high quality -- at least for now. That way, I keep other drug options open down the road, and I can await the results from vaccine and engineered immunotherapeutic approaches.
Hi Dr. Goodman,
Thank you for your insightful article.
I'm a newbie but trying to get as much information about this disease as my husband was diagnosed in August of last year.
Have you ever considered an allo?
Hi Dan!!
I really like the Mayo approach as well. I believe in most effective vs. most aggressive therapy, as the later is often synonymous with most toxic.
QOL is very important and I also agree with you the goal is to maximize that while managing the disease over time and moving along with the new therapeutic options that arise.
letsbeatthis The allo question is a difficult one. It seems the official myeloma world is anti-allo transplant at present, too much risk for the benefit. We did discuss an allo transplant 3 years or so ago and at that time it did not seem very reasonable. Now of course my situation is much worse and I would consider it.
I did ask my doctor about it again last week and she felt that at this point the risk would be very high with not a good chance of disease control and recommended against it. I am curious if other have any experience with this
I also agree with Dan and Suzierose regarding a low toxicity/high qual approach.I'm starting to sense that more than a handful of myeloma specialist are moving in that direction with the many novel drugs and clinical trial results.
Hasn't Dr Berenson been in that camp since the beginning.However,I do realize that he is against auto sct's in most all but a few cases.
I have found that the researchers are the most cynical of the drug companies! But it is a necessary evil for them to be in bed together. Sigh...
I just try to keep focus on they are comprised of individual people who care deeply about the work they are doing.
Hi love reading all the experiences and opinions
Had stc June of 2010. Only in cr for 4 months
Then m spike started rising rather rapidly. I didn't
Do maintenance. My dr started me on doxil velcade
Dex. And then no more doxil. So next has been adriamycin
Velcade and dex and in two rounds. Mspike gone
From 2.7-1.3. Good results anyone else been
On this?
Dear Arnold your article touched my heart and my mind. I thought hard about what to tell you. In Germany (I'm German) they tried mini allo + and experimental treatment (Carfilzomib combined with the CD38 antibody Mor202) with a good effect in heavily pretreated patients. (I'm totally with you, good effect is not "on the ropes".) One of the patients is a good friend of mine - and he's now stable since one year. Another thougt I had is, why doctors could not look in the lab (with your extracted cells from bone marrow) which therapy could be the best in your stage. If you could see me hands, Arnold, you would see my fingers crossed for you!!! Courage, strength and luck for you from over the ocean! Tom
p.s. I would love to read a comment from some experts here. Perhaps the Myeloma Beacon could motivate some of their experts to discuss this urgent situation more intensively!
Tom thanks so much for your kind words. I wish we were closer to the ability to look at our genes to figure out which drug is best, but we are not there yet. Your study with Carfilzomid and antibody sounds interesting and encouraging.
Dan, you asked for other experiences on therapy strategies. After diagnosis, I was on Velcade (as a sales rep, I used to sell to Millennium; after diagnosis, I felt like I could now be their poster child), then Velcade plus Cytoxan. Now I'm on Revlimid plus dex, with Protonix to keep GI issues at bay. Several other health challenges combined have too much risk for a transplant in the near future. I've been very lucky to have had few, if any, side effects, so I'm now back at work. I'm lucky also in that I now work in the hospital where I'm being treated, so I run downstairs for my monthly Zometa, then am back at work in 45 minutes. My oncologist considers me to be in Partial Response stage, since I keep pumping out light chains. I keep forgetting to check my M-spike, but do know that it's much lower than at first diagnosis. So....in answer to your questions, side effects can happen. Then again, we can take aspirin and have side effects. You'll make the right decision for yourself, based on all the information you have access to, and all the feedback you'll get. Good luck to you.
Hi Arnie!
Did you and your docs look into OSI 906 for relapsed MM patients?
http://www.prescription-pharmacy.biz/news/100352/MMRF__APGD_collaborate_to_develop_OSI_906_for/
Dr. Goodman:
Is your myeloma considered low or high risk? Or using the mSMART 2.0 classification:
http://msmart.org/newly%20diagnosed%20myeloma.pdf
is your myeloma considered low, intermediate, or high risk?
Were you aware of your risk level at the time of your original diagnosis? How, if at all, did it influence your treatment decision? And if you discovered your risk level during your treatment did that information influence your subsequent treatment decisions?
Thank you for sharing your experiences.
Pete N
At the time of my diagnosis I did not have any high risk cytogenetic features. That did it part influence my decision to undergo less aggressive treatment at Moffitt and not go through with the Arkansas protocol. Over time with treat myeloma undergoes aquired genetic changes and mine has now developed more high risk features.
Did you consider OSI 906?
osi 906 seems way too early in the process to make a bet on. Also not sure there are any trials open yet. Seems to me there are are things much further along in development to try first. Thanks though
How about the combination of bortzemib, perifosine and dex?
Or this trial sounds promising as it attacks the core problem of stem cell dysfunction:
http://www.evaluatepharma.com/Universal/View.aspx?type=Story&id=247869
Perifosine-bortezomib ± dexamethasone demonstrated encouraging activity in heavily pretreated bortezomib-exposed patients with advanced MM. A phase III trial is underway comparing perifosine-bortezomib plus dexamethasone with bortezomib-dexamethasone in patients with relapsed/refractory MM previously treated with bortezomib.
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