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-dose melphalan (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.
Related Articles:
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
- Selective Digestive Decontamination May Reduce Risk of Infection In Myeloma Patients Undergoing Autologous Stem Cell Transplants
- Number And Type Of Stem Cell Transplants Carried Out Each Year For Multiple Myeloma Vary Markedly Across U.S. Cancer Centers
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
This is great news! I'm looking forward to the day when we have less aggressive options, but its nice to see the path getting a tad bit clearer. Sounds like there is more work to do.
One doc we saw, who doesn't subscribe to SCT in general anymore, told us there was nothing special about tandem, that it was what "everybody" basically gets anyway. Give one, relapse, give another.
He was being somewhat critical and unprofessional, as the proper definition of tandem is that it is an upfront and frontline treatment protocol. One of many choices a patient has to sort through.
This study seems very outdated to me. I underwent single, and will soon be in complete response for 44 months. The use of novel agents has changed the whole picture.
Was interesting to read that if I stay in CR for eleven years..I am cured?! I will post back in seven years....busy with life...haven't felt this good in years.
The results of this study have been rendered doubtful by the clear selection bias of the patients who underwent a second transplant. To obtain valid results, the study should have been run with a control group who didn't receive a second transplant but who satisfied the criteria of eligibilty for two transplants.
Hi Lori, Marc, and Bill,
Thank you very much for your comments.
Marc, the authors of the study agreed that survival times are likely longer now that the novel agents are available. Although this study was conducted more than 10 years ago, it's important to continue following those patients to see how long they remain in remission and how long they continue to live. Results after a brief follow-up often only estimate what the average survival will be and can't begin to estimate whether there will be a plateau in remission and survival rates after many years. This information is also important for those who were diagnosed 10+ years ago and were treated before novel agents were introduced.
Bill, you are absolutely right that additional studies with the type of control group that you described are necessary.
Julie,
With respect to Bills comments on a control group, is that really necessary?
I'm sure a control group could be synthetically created by compiling a pool of patients who had undergone a single transplant and whose demographic/health stats matched those of the patients who had undergone a tandem transplant.
Medo, your suggestion might work. The problem lies in duplicating the exact procedures and selection criteria in different studies.
When I re-read my original post, I realised that I might have given the impression that I don't see any benefit in tandem transplants. I do think that tandem transplants probably increase longevity but it is hard to say exactly how much without a control group.
Julie, I was very surprised that the author of the study had taken time to reply to patients. I really appreciated that.
Greetings All,
My husband was diag. 2 years ago (Dec 18, 2009) but probably had it 2 years prior to that. Had many strange symptoms but never showed up in his blood work. The symptoms finally peeked and very much spine pain that is when MY spine surgeon hit on what it was. Because of his age and heart condition - the oncologist did NOT feel he should have or could handle the stem cell transplant. He has done well on Revlimid-Dexamethasone-Zometa for over two years and we are grateful. His labs have been very stable for 9 months and he has been off the Revlimid and dex for 9 months. Still on the Zometa monthly. We are so grateful to God for every month off the stuff!! .. Many ups and downs, heartaches and trials. We know there is no cure and unfortunately he will need to go back on those awful meds.
We are interested in what is new for us patients who cannot have the transplants. Wish someone would address our concerns for hope.
God bless you all who have mm and those who care for them. We live in Metamora Michigan.
I agree that this study is a bit antiquated, but I am on a trial that included tandem transplants, 3 months apart, with all cells collected prior to first transplant. The first of the 3 arms of the trial consists of tandem transplant with Revlimid maintenance EVERY day for 4 years. The second arm is a single transplant with just Revlimid maintenance and the third arm is single transplant with 4 months of RVD and then the Revlimid maintenance. It will be interesting to see how each compare in the years to come.
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