Some highlights:
* Significantly better 10-year overall and event free survival
* 12 percent of patients still in remission at a median follow-up time of 13.6 years
* Study shows that after 11 years, rates of recurrence were much less likely to relapse later
* Study included alkalyting agents (nasty chemo) but no novel agents (thalidomid, revlimid, velcade)
ALL of this supports BB, UAMS, and Total Therapy. BB refuses to put his patients into a blind trial because he thinks it would be unethical not to use the regimen he feels has the best chance of saving their life in order to prove a point. To my knowledge, this is the first published data of such a trial, and the first document outside of Arkansas that supports the tandem transplant concept.
That makes this extroardinarily important.
EVERYTHING BB was doing when I was diagnosed -- Relvimid in newly diagnosed patients, Velcade in newly diagnosed patients, maintenance therapy -- has subsequently been accepted by the establishment who at the time of my diagnosis said BB was crazy to do it. I've written here that tandem transplants would be the last domino to fall. But now, this data proves him to be right about that as well.
That makes this extroardinarily important.
EVERYTHING BB was doing when I was diagnosed -- Relvimid in newly diagnosed patients, Velcade in newly diagnosed patients, maintenance therapy -- has subsequently been accepted by the establishment who at the time of my diagnosis said BB was crazy to do it. I've written here that tandem transplants would be the last domino to fall. But now, this data proves him to be right about that as well.
I don't normally directly proselytize beyond telling my own story, and to be clear there are some for whom Total Therapy is not the right choice, and there are about 20% of patients who don't respond to any treatment.
But I **URGE** anybody newly diagnosed with this disease to explore the aggressive option. It may just save your life. There is a lot of literature and blogosphere commentary about being conservative -- I am one loud voice to the contrary. Explore your options -- and before considering something like JB's protocol, ask him how many of his patients are still alive after 10 years of treatment. Better still, ask ANY doctor with whom you are talking.
BB will tell you...to the exact number...how many people are alive after any given number of years. Beware any doctor that won't share that information, or sees too few Myeloma patients to keep track of it.
Okay, that's enough. What GREAT news for all of us, though!!!!! :)
Full text of the article copied below.
Long-Term Follow-Up Results Indicate Double Transplantation Is Superior To Single Transplantation For Myeloma
Long-term follow-up results from a clinical trial show that multiple myeloma patients who underwent two stem cell transplants remained in remission longer and also survived longer than patients who underwent one transplant. These findings are updated results from a previously published study comparing single versus double transplantation.
Multiple myeloma patients are commonly treated with stem cell transplantation. Several studies have shown a survival benefit to having a second transplant a couple of months after the first. However long-term follow-up results are necessary to confirm this.
Patients were recruited for the study between 1992 and 1997, and the initial findings were published in 2001. The current report includes updated results of the trial after following the patients for a median of 13.6 years.
The clinical trial evaluated the outcome of 90 patients (46 newly diagnosed and 44 pre-treated) who were planning on undergoing double (also known as tandem) stem cell transplantation using their own stem cells.
Of the 90 patients, 49 patients actually underwent the second transplantation.
Stem cells for the first transplant were collected prior to a preparative conditioning regimen of high-dosemelphalan (Alkeran) and then transplanted back after the melphalan treatment.
Stem cells for a second transplant are often collected at the same time as the stem cells for the first transplant, but some myeloma cells remain in the bone marrow and can be collected along with the stem cells. In an attempt to increase the efficacy of the regimen, this study collected stem cells for the second transplant several months after the first transplant.
Patients who were eligible for the second transplant received conditioning therapy with a combination of busulfan and cyclophosphamide (Cytoxan) and then received transplanted cells that were collected after their first transplant.
At the time of the trial, novel agents, such as thalidomide (Thalomid), Revlimid (lenalidomide), and Velcade(bortezomib), had not yet been introduced for the treatment of myeloma.
In both the original and updated reports, patients undergoing tandem transplantation experienced a median overall survival of 84 months. However, long-term follow-up showed that overall survival of patients who underwent single transplantation decreased from 49 months in the initial analysis to 44 months in the updated report.
Initially, the data showed that patients receiving tandem transplants were likely to have better survival than patients receiving a single transplant. However, only in the follow-up results was the difference between the two groups significant, demonstrating the importance of long-term follow-up of clinical trial participants.
Patients who received tandem transplants also achieved significantly better 10-year overall and event-free survival than patients who received a single transplant (34 percent versus 18 percent for overall survival, and 18 percent versus 0 percent for event-free survival). This data was similar to previous studies comparing single and double transplants.
The researchers noted that at the time of the follow-up analysis, 12 percent of patients who underwent tandem transplantation were still in remission. They also noted a “plateau” in remission rates after 130 months (almost 11 years), meaning that patients who were still in remission at that time were much less likely to relapse later. They attributed this long-term remission to the high-intensity of the regimen, not the use of stem cells collected after the first transplant.
The researchers concluded that the new long-term follow-up data confirm the promising results published in the original report. Additionally, the long-term results show that tandem transplantation is superior to single transplantation.
In their evaluation of the updated follow-up data, the researchers cautioned that it is important to consider a possible selection bias in the trial. Patients with a good prognosis may have been more likely to undergo a second transplant. The primary reasons for not undergoing the second transplant were insufficient stem cell harvest (23 percent, likely due to harvesting after high-dose melphalan), toxicity of previous treatment (9 percent), and progressive disease (8 percent).
For more information, please read the follow-up report in the Journal of Clinical Oncology (pdf) or the initial results published in Bone Marrow Transplantation.
Great news! Looking forward to further substantiate their conclusions with a long, healthy life. Thanks, Nick!
ReplyDeleteNick,
ReplyDeleteThanks so much for this post. I have been following your experience with great interest. While I only had 1 ASCT, we are saving my stem cells just in case. Traditionally T4;14 like myself did not have as good a remission period as others, so my onc is holding me in CR with 10 mg Revlimid.
Nick, I'm still curious about one thing. There is so much data now that maintenance therapy is important and has great results. I know we are all unique and individual. For example, my MM was very aggressive and quite sneaky in it's ability to hide from blood/urine tests.
Still, I have been trying to find out why Kathy G is no longer on maintenance therapy.
Do you plan to be on maintenance? Do you happen to know why she has opted out of it, given so much supporting data?
I'm a bit worried about doing this "for the rest of my life".
Any insight is most welcome, on or off line.
Thanks for this great post.
Hanna -
ReplyDeleteI am on maintenance for three years, consisting of velcade, revlimid and dex. BB has been doing that for a long time (10 years at least, and this particular cocktail and cadence for about five years).
Kathy is an extroardinary case. She has an identical twin, and was the recipient of a syngeneic transplant. This has the advantages of an allogeneic transplant (i.e. curative) without any disadvantages since the cells are perfectly matched. She will not say it because her mission loses urgency if people think there is a cure out there, but she herself is almost certainly cured.
Maintenance is a breeze. I take 15mg of Revlimid 21 days on and 8 days off, plus 1.3mg/m2 of Velcade weekly, plus 12mg of Dex weekly (I can do without the dex, honestly, but I'm sticking with the girl I brought to the dance). :)
You should be aware that BB's data shows that with Velcade, 4;14 translocation is no longer a negative diagnostic factor. Do a search on google for his presentation titled "The Myth of Incurability" (from 2008...things are even better now).
If you have any questions, PLEASE email me at nvandyk1 at earthlink dot net.
Happy Thanksgiving!!
Best,
Nick
Many other cancers, Breast Cancer, to name one, are on long term maintenance therapy after major medical intervention. It is a theory in cancer treatment. And like all things Myeloma it is being debated.
ReplyDeleteWhile LR is doing a 3 year maintenance plan, many continue on something beyond that. My postulate, if you will, is that they learn new stuff during our 3 year maintenance that allows us to stop at some point. The vaccine research is quite hopeful in that regard.
MM treatment is very fluid, with abundant interest in researching. We are lucky in that regard. CR only means it is at undetectable levels with the current testing diagnostics. The prevailing view is that it is still there in your body, thus the maintenance therapy with all the new drugs available. My husband has tolerated the maintenance therapy very well. Some discomfort, but manageable and tolerable. Its more getting over the emotional hump of having to "treat" regularly.
This is very exciting news Nick. I remain hopeful!
Hi Nick-
ReplyDeleteYour readers can learn more about this European study by clicking on the Journal of Clinical Oncology link from last paragraph of The Myeloma Beacon's article. Interesting to note this is a tandem transplant study, not a TT study. Started before novel therapy agents were even available. One would think this is good news for survivors like you who have used new, state of the art induction and maintenance therapies. I will see if I can learn more when I am in Orlando at ASH next week- Pat
Hi Nick,
ReplyDeleteVery exciting news ! I'll email you questions off line and give you an update on Daryll :) Good to know you're doing well !
Nick,
ReplyDeleteI am so happy to learn you are continuing to do so well, although I really had no doubt. YOur initial response to the first transplant was so good it bode well for you finding CR. Keep it up.
A few notes: Tandem transplants were discussed with me here in Denver as a possible option as early as 2006 after I had no response to my first transplant. I elected to go on a velcade trial, which brought my M protein down to .4, but not CR. A second transplant was discussed then but which I chose not to do. I then went on a maintenance dose of velcade in 2007. So these approaches were being used outside of AR well in advance of our meeting in Little Rock late in 2008.
You also know that I have strong disagreement with the Arkansas approach as it wasn't just not effective for me but it permanently harmed me in my view and forced me into my option of last resort: an allo transplant. Fortunately that is going quite well but I am far from out of the woods. Curiously, after receiving more chemo at Arkansas than anyone should be subjected to: VTD PACE for 5 days, followed by 14 days of 4 drugs (which I've forgotten) and then followed by BEAM Super Plus (9 high dose chemo drugs over 5 days) chemo regime before my transplant. My myeloma moved downward only for about a month then returned to its very high levels. The proposed approach after these failures was another round of VTD PACE. After consulting with doctors in Denver, at MD Anderson, and Mayo, and their analysis of all my treatment, and their actually brainstorming a treatment plan for me, the consensus recommendation was a single drug: revlimid (3 months of 15 mg. for 21 days, then 7 days off). That brought my plasma cell levels from 87% to 27%--something 9 high dose chemo drugs couldn't do. My conclusion is that a driven ambition to show the world that rigorous treatment is right can blind one to more effective much less damaging treatment alternatives. There is no doubt BB has been instrumental in moving MM toward a cure. But in my view there is a reason the AR approach is so controversial: poor outcomes often don't stay at AR, but move to a less aggressive approaches with different docs. Thus, these docs see more of the bad outcomes. My better judgment tells me to just shut up and mind my own business. But I guess I feel strongly enough after 5 1/2 years of dealing with an aggressive MM and consulting with the top docs at MDAnderson, Mayo, and Sloan Kettering as well as spending my requisite 4 months being treated in Little Rock, that AR is not the panacea. Some docs will actually talk with you about the pros and cons of their approach as well as the AR approach. In AR my experience was that there was no consideration of any other approach--only to continue to ramp up the chemo. I have said much more than I intended (perhaps its the steroids I'm on) but I would welcome further discussion off the blog.
Best wishes to your family and my deepest wish for your continued good health.
Dan
Wow Nick,
ReplyDeleteDid you really delete my comment?
Dan
Dan -
ReplyDeleteI absolutely did not delete your comment!!! Can you re-post it?
Best,
Nick
Did anyone notice that for the second transplant researchers used stems cell harvested after the first transplant. Does BB's current protocol use this approach?
ReplyDeleteNick,
ReplyDeleteSorry about that. I think my post was too long and it got sent into cyberspace. So let me give the abbreviated version:
I was offered a tandem transplant in 2006, 3 months after my first transplant showed no response. I declined and went into a clinical trial with velcade. While I didn't achieve remission the velcade/dex worked well enough that I went on maintenance velcade/dex in 2007 for most of the year. My doc here in Denver often works with the myeloma docs at Dana Farber, MDAnderson and Mayo. They were all aware of BB's tandem transplant approach and did not think it crazy, but the data was not complete. The same is true for the maintenance regime. As noted, I was offered the tandem in 2006 and on maintenance in 2007. BB's statistics for treating initially diagnosed low risk patients with tandem transplants is very impressive.
But there is a big BUT. There is no other similar population in any other institution with which to compare his stats. No one does the gene profiling studies so they don't have stats of that population. As you know, my experience at UAMS was quite different than yours--understanding that I had received extensive treatment for 4 years prior. There are significant risks with the very aggressive UAMS approach and you won't hear about them at UAMS and maybe not even from your own doc. But if you are one of the unfortunate ones for whom the approach doesn't work, any future treatment has been significantly compromised. After the failure of the aggressive treatment I received my only remaining option was an allo transplant. Fortunately my brother was a match and things are going well so far. I have to stop or this will apparently self delete.
My best to you and your family and I am very happy you continue to do so well.
Dan, thank you! Your comments are an important cautionary tale. As I have tried to mention here, BB's approach to low-risk, newly-diagnosed patients is one thing. I am less convinced that Total Therapy is the right approach for those who have been treated extensively elsewhere. As your experience attests, it can be a much more challenging situation and the carpet-bombing approach can do more harm than good.
ReplyDeleteI wholeheartedly advise people to do their own research and should they go to Arkansas -- for whatever treatment -- they should ask BB directly the tough questions that I asked him (e.g. "why don't you put people in trials?" "what incidence of long-term marrow damage has there been?", I went through each induction drug with him and asked about incidence of the particular side effect, etc.)
I am delighted to hear of your improvement and response to the mini-allo! Keep on keepin' on, my friend!
Pete, BB harvests stem cells only once. He does not believe there is a difference between harvesting after high-dose melphalan. Also, they tested irradiated stem cells versus those not treated with radiation and found no difference in residual cancer cells. Basically, consolidation and maintenance will take care of stragglers, is his point.
ReplyDelete
ReplyDeleteCANCER CARE