Early Stem Cell Transplantation May Improve Survival In Newly Diagnosed Multiple Myeloma Patients (ASH 2010)
Patients under age 65 who undergo autologous stem cell transplantation early have significantly higher survival rates than patients who receive continued treatment with Revlimid and dexamethasone, according to a retrospective analysis of a recent clinical trial.
However, Dr. David Siegel, from the Hackensack University Medical Center in New Jersey and lead investigator of the study, pointed out that these results need to be interpreted cautiously, because the patients were not randomly selected to receive either an early or late stem cell transplant.
The results do suggest, however, that early transplantation may be beneficial for younger patients. In addition, the results seem to call into question the commonly held belief that transplantation should be used more as a last resort in older patients.
“I think that we really have to seriously consider the role of transplant. As much as we think that we have data that obviates that, these observations would tend to argue against that. There is something to be said about early transplants,” said Dr. David Siegel, when he presented the study results at the American Society of Hematology annual meeting in Orlando last week.
Research has demonstrated that novel therapeutic agents, such as Revlimid (lenalidomide) and Velcade (bortezomib), significantly improve outcome for newly diagnosed multiple myeloma patients. Prior to the development of these agents, many myeloma patients underwent autologous stem cell transplantation as a frontline treatment.
Stem cell transplants involve collecting a patient’s stem cells from their blood. After undergoing high-dose chemotherapy, the patient receives the harvested stem cells back, which replace the cells that were damaged or destroyed in the chemotherapy process.
In order to determine the effect of early transplantation on patient outcome, Dr. Siegel and his colleagues analyzed the results of a recent clinical trial in which newly diagnosed myeloma patients were randomly assigned to one of two treatment arms: Revlimid with high-dose dexamethasone (Decadron), called RD, or Revlimid with low-dose dexamethasone, abbreviated as Rd. After completing four treatment cycles, patients had the option to undergo an autologous stem cell transplant or to continue the assigned treatment.
An initial analysis of the data indicated that patients who underwent early stem cell transplantation, i.e. after four cycles of Revlimid-dexamethasone treatment, had a significantly higher three-year overall survival than patients who did not undergo early stem cell transplantation (92 percent versus 79 percent).
In his presentation last week, Dr. Siegel showed data comparing the survival outcomes for three different patients groups: patients under age 65, patients ages 65 to 70, and patients over age 70.
For each age group, patients were subdivided into those who underwent early stem cell transplantation and those who did not.
For patients under the age of 65 who did not undergo early stem cell transplantation, the overall survival was 94 percent for one year, 88 percent for two years, and 78 percent for three years. For patients under age 65 who underwent early stem cell transplantation, the overall survival was 100 percent for one year, 94 percent for two years, and 94 percent for three years.
“I recognize and I emphasize that this is not randomized data. But this is a large patient population that was transplanted in the era of novel agents… Overall, there is a statistically significant advantage to early stem cell transplantation in patients under the age of 65,” said Dr. Siegel.
Although similar trends were observed in the age 65 to 70 and over age 70 groups, these results were not statistically significant, as the patient populations were smaller in these two groups.
In all age groups, the one-year patient survival was notably high across the board. However, the patient survival for patients treated with RD significantly decreased at two years if patients did not undergo early stem cell transplantation. This same drop in survival was noted for patients treated with Rd at three years if they did not undergo early stem cell transplantation.
In evaluating the differences in patient survival among the age groups, Dr. Siegel and his colleagues hypothesized that treatment-related deaths would be higher in the older age groups (age 65 to 70 and over age 70).
However, for patients age 65 to 70, there was little difference in the one-year survival rates (94 percent for no early stem cell transplantation versus 95 percent for early stem cell transplantation).
For patients over age 70, the one-year survival rates were also comparable between the two stem cell transplantation subgroups (92 percent for no early stem cell transplantation versus 100 percent for early stem cell transplantation). However, Dr. Siegel cautioned that the sample size for this population was extremely small (only six patients).
In noting that the selection bias of the stem cell transplantation subgroups limited the data analysis, Dr. Siegel and his co-authors emphasized a “need for randomized trials investigating the timing of autologous stem cell transplantation in myeloma in the era of novel therapy.”
For more information, please refer to abstract 38 at the American Society of Hematology Meeting website.
Related Articles:
- Selective Digestive Decontamination May Reduce Risk of Infection In Myeloma Patients Undergoing Autologous Stem Cell Transplants
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
- Early Use Of Radiation Therapy Associated With Shorter Survival In Multiple Myeloma
- Number And Type Of Stem Cell Transplants Carried Out Each Year For Multiple Myeloma Vary Markedly Across U.S. Cancer Centers
I have several problems with this. First, this study doesn't compare life expectancies of patients who wait to, then later transplant. Are transplants less effective when a patient waits?
Secondly, what was the genetic make-up of the patient population? How many patients had chromosome deletions or translocations which would identify them as high risk?
Finally, if stem cell transplants worked so well, why are life expectancy numbers, especially for low risk patients, rising so quickly? After all, if that is the way it "used to be done," why are survival numbers rising now with more patients putting off transplants?
I am a member of three large support groups, totalling over 80 patients. One group member has died over the past three years. One! Even several younger, high risk patients with aggressive disease have survived three years. What is wrong with these patients (or their care) who are dying? Do they have other underlying health problems?
If it really is best to transplant early that's fine. I just don't think this sample proves anything.
Pat
The author stated that more analysis and studies needed to be done. It is not definitive, like almost all of the studies done on Myeloma. But it is excellent that folks have finally been trying to piece together some sort of analysis on this subject since there is such a debate about it.
And the reason the low risk patient numbers are rising so rapidly is because of the new drugs used, just like for people like who choose not to transplant. Ten years ago you would not have had much of a choice because the drugs were limited. Its not the transplant that is the treatment, that is the recovery. Recovery from very high dose chemotherapy (i.e., the cocktail of drugs both old and new used to wipe out your immune system and bone marrow).
Interesting web link on the "timeline" of MM drugs as approved by FDA ( http://bit.ly/i0sCWi ). For instance you will notice that Velcade, though approved in 2003, was approved for patients who were TWICE previously treated and in relapse, not as part of frontline treatment. Anyway, would love to have a comprehensive timeline history on MM drugs available when and for what. Seems like we have enough history to have such a comprehensive timeline.
I find reading these studies doesn't satisfy what I want to know about the patients: male or female, race, other co-morbities or health problems, and especially, the genetic makeup of the myeloma cells.
So I can't interpret what these studies mean, other than some researchers got their data in on time for publication. When I feel so great now, despite having MM lurking about, am I to think I have only months to live? Suzanne
Suzanne, this is what I wrote about this on my blog, that might address your concern, at least I hope it helps. Its only a point of view, agreeably, mine.
"And remember, this is important, for those of you who have chosen a particular path, don’t second guess yourself or your decision. You made the right decision for you and your family at the time you made it, with the information & advice given to you. Its really important to not read these articles and think you did something wrong, “blew it”, whatever. I don’t even like seeing them to be honest, but I understand clearly it is part of the ongoing research needed for finding better treatment options for those newly diagnosed. And trust me, there are just as many that say Dave and I were brilliant to do what we did as there are that say what SUCKERS we were to take the path we chose! So try to keep yourself grounded on such matters. Besides, this article states more analysis needs to be done and it does. It won’t matter one way or the other for those of us who have already been diagnosed, treated, and are on our particular treatment path. As Dave is fond of saying: 'The Horse has Left the Barn!'"
Oh for Pete's sake, everyone. We all know that genetic characteristics are going to influence the outcomes for individual patients in this study, and gender and race may as well. And it's a given that, because this research was not a controlled trial with random assignment to different arms of the trial, we can't draw any definite conclusions based on the results.
But take a minute or two and look at the actual research abstract. The authors lay out just as much data and results as you are probably permitted to put in an abstract.
And, say what you want about genetic abnormalities, gender, race, age, etc., the facts are: Of the almost 70 patients under 65 who got an early transplant, the three-year survival rate was 94 percent. Of the over 140 patients under 65 who did NOT get an early transplant, the three-year survival rate was only 78 percent.
If we were talking really small samples, differences in genetic abnormalities, gender, race, age, etc, might be able to explain that difference. These samples, however, are pretty big. Not huge. But pretty big.
Also, I think the data may make an even stronger case for early transplant than it seems at first glance. What if patients in the trial who were higher risk tended to get early transplants more often than patients who were lower risk? Then the fact that survival rates are so high among early transplant patients is all the more impressive.
So, yeah, let's agree that the data aren't perfect. But let's also agree that they are definitely interesting and they suggest the question of transplant vs. don't transplant is far from dead.
Interesting. I wonder if this could have to do with early stem cell harvest versus late stem cell harvest rather than the timing of the transplant? Because we do know that after being on certain drug therapies for extended periods of time it is harder to obtain a successful harvest. Possibly the later transplant patients are being rescued with less than optimum stem cells?
Merry Christmas to all of my fellow MM colleagues!
It's just nice to know, no matter what any final study may show, that so much progress is being made vs. just 10 years ago. We are all different, and we're all hoping that the numbers we read seem to look better for our own particular choice of treatment. That's normal, although we do wish the best for all those facing MM.
I'm just happy to read that efforts are being made to help all of us with these studies. In closing I would just like to say that I sincerely hope that all of my fello MM brothers and sisters feel well enough to enjoy this Holiday Season, and may God bless you all.
My most annoying problem currently is with Nurapathy(sp) pain in my feet and toes. If anyone out there has a treatment or medication that works well for them I would appreciate your input.
Thanks, and always remember the people that face diseases far worse than MM. It helps me to not feel too sorry for myself !
JP
HI John, Don't know if you have already looked into this, but I posted on my blog what we do and then linked to Myeloma Hope (Don's Blog) as he has listed several major cancer center's remedies. Perhaps you can find some help in these links. Basically one of the causes in a healthy person is a Vit B deficiency, so that is while you will see lots of Vit B type supplements being prescribed. Anyway, hope this helps you find an solution for your PN.
Hi John,
You may also want to check out tips that people have posted to the Beacon forums. For instance, there are discussions about preventing peripheral neuropathy and treating existing neuropathy.
Additionally, the Beacon wrote an article about the causes and treatments for myeloma-related peripheral neuropathy earlier this year.
I am very worried about my husband health ,he was diagnosis with mutiple melioma. I want u to help me what i can do , he is sixty years.