Transplantation Versus Novel Agents For Myeloma: Study Supports Transplantation (EHA 2011)
As the myeloma community continues to investigate whether stem cell transplantation or novel agents is the best way to treat newly diagnosed myeloma patients, recent results from a Phase 3 clinical trial indicate that stem cell transplantation may lead to longer disease-free survival.
The results from this study show that more multiple myeloma patients who received a stem cell transplant were alive and disease-free after 24 months compared to patients treated with Revlimid in combination with conventional chemotherapy.
The transplanted patients, however, also experienced more severe side effects compared to non-transplanted patients.
Dr. Antonio Palumbo, the lead author of the study from the University of Torino in Italy, presented the results at the 16th Congress of the European Hematology Association (EHA) in London on Sunday.
Novel agents have improved myeloma treatment in recent decades, prompting researchers to investigate whether they may be as effective as stem cell transplantation in myeloma patients.
According to Dr. Palumbo, these results are the first to show that stem cell transplantation may be superior to novel agents for progression-free survival in myeloma patients.
Dr. Palumbo’s study included 402 newly diagnosed myeloma patients under the age of 65. All patients received four 28-day cycles of initial therapy that included 25 mg Revlimid (lenalidomide) daily for three weeks and low-dose dexamethasone (Decadron) weekly.
After their initial treatment, half of the patients continued with six 28-day cycles of conventional chemotherapy plus novel therapy, which included melphalan (Alkeran) and prednisone plus 10 mg Revlimid daily for three weeks (MPR).
The other half received two courses of high-dose melphalan, plus cyclophosphamide (Cytoxan) and granulocyte colony-stimulating factor to increase the number of stem cells prior to collection. This was then followed by stem cell transplantation.
After a follow-up of 12 months, interim results of the Phase 3 trial presented last June suggested that conventional chemotherapy in combination with Revlimid may be as effective as stem cell transplantation (see related Beacon news).
After 24 months of follow-up, patients who received MPR achieved a similar complete response rate (20 percent) compared to patients who received a stem cell transplant (25 percent).
However, fewer patients who received MPR were disease-free at 24 months (59 percent), compared to patients who received a transplant (75 percent).
Overall survival remained high in both the MPR group (95 percent) and the transplanted group (97 percent) after 24 months.
The most common severe side effect was low white blood cell counts, which affected 55 percent of patients who received MPR and 89 percent of patients who received a stem cell transplant.
Patients who received a stem cell transplant also experienced higher rates of infection (17 percent versus 0 percent) and stomach and intestinal side effects (21 percent versus 0 percent), compared to patients who received MPR.
For more information, please see abstract 508 on the EHA website.
Related Articles:
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
- Once-Weekly High-Dose Kyprolis Yields Deeper Responses And Longer Remissions Than Twice-Weekly Kyprolis (ASCO & EHA 2018)
The content of the article does NOT seem to support the articles title It would appear to me that the data presented here makes the two choices sort of "6 of one, half a dozen of another".
Hi Steve,
Thanks for your feedback.
Certainly the debate over stem cell transplant versus novel agents for newly diagnosed myeloma patients is not over. Longer follow-up and more studies are needed.
Researchers have been hoping to show that novel agents are as or more effective than stem cell transplantation, which has a higher rate of side effects and requires a long recovery period. However, given that stem cell transplantation significantly extended disease-free survival in this study, the researchers were not able to conclude that novel agents are as effective as stem cell transplantation. Until novel agents are proven at least as effective as stem cell transplantation, many myeloma specialists will continue to prefer transplantation for newly diagnosed myeloma patients.
Long term survival and quality of life seem far more imperative to me than an increased probability of being disease-free for an inevitably finite time. After 24 months, there is no significant difference in longevity between the two groups. However it seems fair to conclude that the novel agent group's quality of life was significantly better than the SCT group's experiences in the first 24 months. Only time will tell whether a better quality of life and the avoidance of the harsh chemicals used in SCT's will yield a longer life. So at this point in time, the choice comes down to picking a higher quality of life for the first 24 months or gambling that an SCT will significantly improve one's chances for a significantly longer life.
Steve is correct; the title of the article is NOT supported by the content.
Agree 100% with Harvey. Guess we would have to look at overall survival down the road to see if the extra side effects are worth it. Ironically enough at the point in time there will be some newer treatments to change the landscape yet again. That as I see is a good thing.
I have noticed too that the information in the article does not match the headline. The biggest issue here is progression free survival versus overall survival. The abstract from the EHA basically reads: Conclusions: PFS was significantly prolonged in MEL200 group compared to MPR, although toxicities were significantly higher. This is the first report showing a PFS advantage for ASCT in comparison with combinations including novel agents. At present OS is not significantly different in the two groups.
An interesting fact that the Beacon's article fails to mention is that a review of the underlying abstract reflects that among patients that achieved a CR - the rate of PFS was essentially equal in both cohorts. Thus for patients who achieve CR through novel agent therapy, the data seems to support the argument that there may be no known added benefit to undergoing ASCT.
Eleven years after my SCT, I am still maintenance free.
I have followed the development of all the new drugs since 1999 and I find it extremely hard to believe that the MPR group had 0 infections and a higher white blood count.
My pre-induction therapy was VAD so perhaps the more common current use of the "novel" therapies should be re-evaluated if they have long term negative effects.
There is no comparison of my quality of life versus ongoing maintenance in time spent, travel costs, a variety of side effects and not to mention the stress in dealing with the cost of the drugs and Medicare and the insurance companies.
A few years ago, research was published showing that the survial and disease free times were greatly improved if the pre-induction therapy showed little or no MM.This report does not address this issue.
Oh, please! Yeah, maybe the headline to this article should have emphasized the disease-free survival data rather than making a more blanket "supports transplantation" claim.
But that's a definite "maybe."
The fact is that the disease-free survival data are clearly in favor of transplantation, and the overall survival data are trending in that direction, even if they haven't gotten to the point of being statistically significant yet.
And remember, we're not talking here about older patients. These are patients young enough and physically fit enough to be able to undergo a stem cell transplant. That means that they also are patients who would really benefit from extended survival, even if it involves a short-run reduction in quality of life.
We're NOT talking here about older patients who are so frail and already have limited life expectancy that quality of life is especially important.
So it's perfectly understandable that the Beacon would choose a headline that focuses on the survival impact of the two treatment approaches. If you focus on survival, the transplantation approach definitely looks like it will be the winner in this race.
And, Stephan, what's so surprising that the patients who achieved complete response in both study arms had similar survival rates? That's not unusual, and it's why achieving as good a response as possible is usually a key treatment goal. The important thing is that more patients in the transplant arm achieved a complete response compared to the non-transplant arm of the trial. (According to the abstract, the complete response rate was 20% in the non-transplant arm and 25% in the transplant arm.)
My observation, with my husband doing a Tandem, is that the mental anguish and stress and many side effects of patients choosing the novel therapy route are not very different from the SCT route,and in some ways it seems even more stressful. Longevity, quality of life, recovery, age, overall health, goals, are all still individually the difficult decisions each patient must weigh in their choice at this time.
We are still very happy with our decision with the goals we hoped to achieve in treatment. Continuing to find ways to minimize risks, long term and short term, side effects, longevity while maintaining quality of life is a endeavor I am always glad the researchers and physicians are continuing to explore. I fully expect that some time down the road, SCT may not be necessary to achieve certain goals, but I don't see any definitive research yet that bears that out, hands down. It may never bear it out for some of the high risk and ultra high risk presentations of MM. Right now, I wish that more institutions were engaging in the GEP (Gene Expression Profiling) before patients are advised in making their choices. The low risk group is projected a 15 year life span with tandem transplants in Little Rock for over two years now. UAMS focus is now almost exclusively on the high risk and ultra high risk groups and working to give them better information and treatment response. It frustrates me at times that these articles and research are not differentiating these patient groups in their studies. I think its imperative that they do so to have better understanding.
I am hopeful real break throughs are in the making and hopeful that the SCT will be tossed aside, as it is arduous, at least for the low risk group!
Since when is melphalan a novel agent? This study simply compares the levels of melphalan and it should be no surprise that some patients do as well with less melphalan(novel agents?) than with more melphalan(Stem Cell transplants)
The only useful comparison should include the truly novel agent Velcade. Let's try and ditch the hyper poison melphalan ASAP.
Gary, after the same induction therapy that patients in both arms of the study received, the patients in the non-transplant arm received melphalan, prednisone, and Revlimid (MPR). Revlimid is generally considered one of the three "novel" agents used in myeloma treatment, the others being thalidomide and Velcade.
Instead of receiving the MPR regimen, the transplant patients received high dose melphalan plus cyclosphosphamide and GCSF and then had their transplants.
So, in this study, the patients who received particularly high doses of the "hyper poison" melphalan actually had the longest survival.
Maybe that's why melphalan was considered such a breakthrough in myeloma treatment back when it was introduced a few decades ago.
TerryH - there is absolutely nothing surprising about the fact that those patients who achieved CR had similar PFS rates irrespective of whether they underwent an ASCT or followed up with a less burdensome regimen. The point is that although it's true that an ASCT increases the likelihood that a patient will obtain CR, this study appears to confirm other data indicating that if a patient achieves CR via drug therapy consolidation with ASCT for that patient may be unnecessary.
I find it interesting reading the comments on this article from yesterday and then reading the comments on the Beacon article from today: http://www.myelomabeacon.com/headline/2011/06/16/pats-place-overcoming-my-life-long-fear-of-giving-myself-an-injection/
Basically, in response to this article, everyone's complaining about the side effects and toxicity of the stem cell transplant process. My guess is most of you have chosen not to undergo one.
The article I linked to is on a totally different topic, but the connection is that it's written by a man who's planning to undergo a stem cell transplant soon. Many of the comments are from people who said their stem cell transplant really wasn't that bad or that they feel much better since their transplant.
Maybe they're just trying to be reassuring, but I find it so much more useful to listen to what people's experiences were really like rather than concerning myself over an extra 10-20% of people getting a certain side effect with one drug combination compared to another. Who cares if it's not that bad.
Who hasn't taken aspirin for a headache despite the fact that it can cause stomach problems. If it's the best at treating the problem, especially when we're talking about myeloma here, then that's what I'll choose.
Granted, we're all entitled to our own opinions when it comes to weighing the pros and cons of different treatments. I'm glad you all believe in your choices. Make a decision and don't look back. But respect others' choices too, especially considering each of our diseases is different and the information and options are thankfully changing rapidly. No two of us will do it exactly the same way.
Frank: You call it "complaining". I call it an intellectually stimulating conversation. I find the communication back and forth -- pro and con -- fascinating. We really have some smart MM patients out there. Be well everyone.
I guess transplants are a hot topic right now at The Beacon. Not only is there a lot of discussion here on this article and on the column Frank links to, but there's also a very relevant discussion going on over at the Beacon's forums. Here's the link:
http://www.myelomabeacon.com/forum/stem-cell-transplant-and-ability-to-do-light-work-t464.html
The discussion was prompted by a forum member asking how much a transplant affects a person's ability to do work. Other forum members have shared their transplant experiences, often in a lot of detail. It's good reading.
It is a shame that a third study was not run alongside the above two studies, using Cyclophosphamide-Thalidomide-Dexamethasone (CTD), which was mentioned in The Beacon in March 2010 as a promising first line treatment prior to stem cell transplant: http://www.myelomabeacon.com/news/2010/03/19/cyclophosphamide-thalidomide-dexamethasone-combination-is-promising-as-first-line-treatment-for-myeloma-prior-to-stem-cell-transplant/
I assume the problem with introducing a third category into the test probably came about as it was paid for by certain drug companies who hoped to prove that buying their novel agents gave a better response or survival rate using their products.
I suspect there may be a few people out there on CTD who would be interested in that comparison.
My husband Dave, worked throughout his tandem transplant at Little Rock, the better part of a year on and off. He worked full time up on his return, albeit sometimes at home and off hours. We chose to do his collection and first transplant over the holidays from Thanksgiving through New Year's which enabled him plenty of "down days" with people in the office taking off for holidays. He is an engineer/manager so not a physical labor sort of job. Everyone at his company helped him through the process and understood when he would say, "could you refresh my memory..." the whole chemo brain issue.
As far as elderly doing transplants, there are many at Little Rock that are well over 70 receiving their treatment. It is no doubt very hard, but totally doable, if they are relatively healthy going in. It is always very frustrating to me when folks assume that you are decrepit because you are 75 or something when your quality of life is excellent. You can't base it solely on age.
I am with Harvey: My biggest gripe about the approach of this study is that is measures success based on "disease-free survival." As far as I can tell, all that means is that the patients did not have detectable myeloma in their marrow or protein in their blood. This is a cold clinical measurement that I am still struggling to reconcile with quality of life. Or overall survival.
Indeed, the patients who received transplants in this study had lower white blood cell counts than the MPR group -- and they also had higher infection rates and side effects (intestine and stomach) that (apparently) were not seen at all in the MPR group.
How is that success? I keep going back to the majority of MGUS patients, who despite having significant bone marrow involvement and M-protein levels, never progress -- despite their "disease." It seems to me that understanding why these individuals do NOT progress may be the key.
That said, I do know that this is complicated and frustrating. But to me this study is disingenuous and deceptive.
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