Yesterday in Part One of my post, patient reader (and now contributor) Bill O’Halloran shared the first steps in his decision making process about whether to undergo an autologous stem cell transplant–or possibly two.
Let’s resume Bill’s analytical journey as he examines the pros and cons of transplanting now or later:
Autologous Stem Cell Transplant (ASCT) Decision Making Process: The Pros and Cons of Early vs. Delayed ASCT
The standard treatment of choice for younger patients with Multiple Myeloma is to undergo 4-8 months of induction therapy using a combination of the newer novel drugs, followed by an ASCT. It is well known that achieving a Complete Response before the transplant leads to a significant survival advantage over those who did not achieve this. The increased efficacy of these new drug treatment regimens has resulted in more patients achieving higher levels of response, with many patients achieving Complete Response or even stringent Complete Response. With these higher response rates, the front-line drug treatment alone may provide extended remission times. This has given rise to the question as to whether it might be better to defer the ASCT until after first relapse.
December was a good time to start my research, as the American Society of Hematology (ASH) was about to hold its annual meeting in San Diego. Literally hundreds of papers were being presented on all aspects of Multiple Myeloma, from promising new drugs to transplant issues. Furthermore, Dana Farber was sponsoring a patient symposium in late December, gathering myeloma experts from the New England area.
There is very little data available on this topic. There is a major clinical trial currently underway (TX81759) addressing the question of early vs. delayed ASCT, but it will be several years before definitive results are available. In the meantime, there are conflicting data and opinions. Some of the more relevant results of my research are as follows:
* In a September 2011 paper (Ref. 2), Dr. Shaji Kumar of the Mayo Clinic summarized a retrospective study of 300 patients, and concluded that based on the results, stem cell transplant “can be deferred until second line.”
* At the recent ASH Meeting, M. D. Anderson’s Dr. Robert Orlowski was interviewed about whether new novel therapies will someday replace auto stem cell transplants. He responded with a qualified “yes.” Dr. Orlowski clearly believes stem cell transplants will become a less important part of myeloma therapy someday. “And when would that be?” a reporter asked. “Not until a number of these newer drugs become available in five or ten years,” he answered.”
* In a poster session at the recent ASH Meeting (Ref.3), Dr. Antonio Palumbo, MD of the University of Torino in Italy, summarized a Phase 3 study of early transplant vs. no transplant with 402 patients as follows: “Progression Free Survival was significantly prolonged in the early transplant group compared to the deferred group. This is the first report showing a Progression Free Survival advantage for ASCT in comparison with conventional therapies including novel agents.”
Dr. Richardson pointed out this last paper to me as another rationale for my opting to do the stem cell transplant now rather than wait.
I then attended the Dana Farber Patient Symposium on December 17. There was a panel discussion on the role of stem cell transplants. The overall consensus of the group was:
* Be as aggressive as possible in trying to contain the disease up front. Don’t hold anything back in reserve for the next relapse.
* ASCT is effective either up front or after 1st relapse. After that, its effectiveness diminishes.
* Achieving Complete Response before ASCT leads to much greater Progression Free Survival and is a relevant objective for myeloma treatment.
Based on the above research, one could conclude that opting for an early transplant might be the best option. However, there is another side to this story that I did not find in my research, especially for younger patients who may face becoming resistant (refractory) to the drugs they are taking, as well as dealing with the possibility of multiple relapses in the future.
As Pat Killingsworth likes to say, “Multiple Myeloma is a marathon, not a sprint.” There is an argument to made that you might not want to expend too many of your bullets up front, running the risk that there won’t be enough left in the chamber in the future when they may be needed.
As of now, there are not many new myeloma drugs being approved by the FDA. The last one was Revlimid in 2007. Despite the many promising drugs currently in clinical trials (including MLN9708), only two myeloma drugs are expected to be FDA approved over the next couple of years: carfilzomib, a proteasome inhibitor that could replace bortezomib; and pomalidomide, an immunomodulator drug that could replace lenalidomide. All the others are 5-7 years away from FDA approval.
In the interim, the only way to get access to these is through a clinical trial or compassionate use. Will these new miracle drugs be available in time to help patients who become refractory to the currently available drugs? Questions like this may give you pause to using up one of your transplant options too soon.
There are other considerations for electing an early stem cell transplant. These could include response to the front-line therapy, general health (heart, lung, kidney, and liver function), career considerations, financial considerations, etc. However, these issues are beyond the focus of the current discussion.
Up until now, I have focused the discussion on younger patients (age 65 or less). This was deliberate in order to address the issues of concern for the broadest possible audience for this discussion. Now I will focus on my own situation at age 69. The dynamics and decision choices are substantially different for me than for a younger patient.
It is preferred to perform ASCTs on patients under the age of 70. This limit may be pushed up to age 75 if the patient is physiologically healthy. My time is running out. My transplant window is less than 6 years. For me, this is a sprint, not a marathon!
Let’s assume that I will be able to harvest enough stem cells to support two stem cell transplants. In that case, if I defer doing the ASCT now, I will still likely only have one more option for a stem cell transplant in the future, if that. Therefore, using one of my bullets to do a transplant now will very likely not remove any future options!
As of now, I am healthy enough for a stem cell transplant. Testing has shown that my heart, lung, kidney, and liver functions are within normal ranges or above average. However, as I progress into my seventies, there is no guarantee that that will still be the case.
In coming to my decision, I based it on the following considerations in descending order of importance:
* Dr. Richardson’s strong opinion
* My age…either do the ASCT now or possibly never
* The Palumbo study showing better results for early transplant
* The Dana Farber Patient Symposium consensus to be as aggressive as possible up front
Therefore, I decided to go for it, and I signed up for the ASCT clinical trial. I feel very confident that I made the right decision for myself, and I have had no second thoughts.
I continued my MLN9708 protocol through Cycle 7. That turned out to be very beneficial, as I finally achieved a Complete Response. I nearly achieved a strict Complete Response, but flow cytometry of my bone marrow aspirate indicated the possibility of minimum residual disease.
On March 13, I went in to Brigham and Women’s Hospital to harvest my stem cells. After 3 days, about 10 million/kg were collected, enough for Dr. Richardson to use for two transplants. Thus, I still have one transplant in the arsenal for the future if needed.
I also got good news about the transplant clinical trial. I was randomly assigned to Arm 2, which involves a single ASCT with several cycles of consolidation with Velcade, Revlimid, and dex, followed by maintenance with Revlimid. Dr. Richardson was very pleased and is convinced that this is by far the best arm of this clinical trial!
Here’s how I view this. I’m being as aggressive as possible in trying to contain this disease up front.
The stem cell transplant may further deepen my response to achieve stringent Complete Response. That would be the ideal result, but I won’t know until my next bone marrow biopsy in 3 months. In the meantime, the consolidation therapy may do the trick if the ASCT doesn’t. I don’t think I could hammer on this any harder if I tried.
An added bonus to this treatment regimen is that I will be on long-term Revlimid maintenance. It has been well established that Revlimid overcomes the poor prognosis associated with my high-risk t(4;14) translocation. It seems that I may be getting the best of all options. I feel very fortunate.
I received my stem cell transplant on March 20, the first day of spring. How appropriate to usher in the season of rebirth and renewal with my own rebirth and renewal. Happy Birthday to me! Everything went well and I am now home recovering. I am hopeful that all this will work out and I will go into a sustained remission for a long time.
I hope this discussion has been of some help to those of you contemplating a stem cell transplant. If you have any questions or would like to discuss any of this further, feel free to contact me, Bill O’Halloran, by email at firstname.lastname@example.org.
Cyber Reference Links
Once again, special thanks to Bill for taking the time to organize his thoughts and re-visit how and why he arrived at the decision to transplant right away.
You may not agree with his decision, but the man cannot be faulted for the way he systematically approached his new, unwelcome challenge.
Good luck to you Bill! Please send along an update from time to time so we can continue to follow your progress.
Feel good and keep smiling! Pat