Revlimid Maintenance Therapy After Donor Stem Cell Transplantation Is Not Recommended For Multiple Myeloma Patients
Results of a recent small Phase 2 study conducted in the Netherlands suggest that Revlimid maintenance therapy improves responses in multiple myeloma patients receiving “mini” donor stem cell transplants. However, the study authors also observed a rapid onset of graft-versus-host disease in these patients after the start of Revlimid treatment.
Based on these findings, the study authors recommended against Revlimid maintenance therapy for myeloma patients receiving “mini” donor stem cell transplants.
“Acute graft-versus-host disease is a life-threatening complication after donor stem cell transplantation, and our primary aim of the article was to warn the myeloma community about this [risk],” the study’s lead author Dr. Monique Minnema of the University Medical Center Utrecht in the Netherlands told the Myeloma Beacon.
“In my view, patients should not be treated with Revlimid maintenance after donor stem cell transplantation outside of clinical trials. If [clinical trials] are to be designed, another strategy has to be followed, like the combination of Revlimid with dexamethasone,” she added.
Donor (allogeneic) stem cell transplantation is the process in which a patient receives high-dose chemotherapy followed by an infusion of stem cells from a matched donor to replace the stem cells destroyed during chemotherapy.
Donor stem cell transplantation may give myeloma patients with advanced disease a better chance for long-term remission than transplantation with their own cells. However, donor stem cell transplantation is also associated with high rates of transplant-related complications, including graft-versus-host disease (GVHD), in which the donor cells attack the recipient’s own cells.
A new strategy known as non-myeloablative (“mini”) donor stem cell transplantation has been shown to decrease the risks associated with traditional donor stem cell transplants by using lower doses of chemotherapy and radiation in preparation for the transplantation.
Past studies have shown that thalidomide (Thalomid) and Velcade (bortezomib) maintenance therapy may improve response in myeloma patients following donor stem cell transplantation without aggravating GVHD.
Two recent studies indicated that Revlimid (lenalidomide) maintenance therapy increases the time to disease progression in myeloma patients following autologous stem cell transplantation (see related Beacon news).
In this study, the Dutch researchers investigated whether Revlimid maintenance is effective in myeloma patients receiving a “mini” donor stem cell transplant.
The study included 30 newly diagnosed myeloma patients with a median age of 53 years.
All patients received three cycles of induction therapy followed by stem cell mobilization with cyclophosphamide, one cycle of high-dose melphalan (Alkeran), and a stem cell transplant with their own cells. All patients also received a “mini” donor stem cell transplant two to six months after receiving the first transplant.
After a median of 12 weeks following the second transplant, they began maintenance therapy with 10 mg Revlimid daily for 21 days in successive 28-day cycles. Patients were scheduled to complete 24 cycles of Revlimid maintenance, but ultimately completed a median of three cycles.
Patients also received medication to suppress the immune system, called immunosuppressive therapy, and to reduce the patients’ risk of developing GVHD. Immunosuppressive therapy was gradually reduced after the first two cycles of Revlimid maintenance in the absence of GVHD.
After a median follow-up of 22 months, 37 percent of patients improved their responses with Revlimid maintenance therapy.
The progression-free survival rate one year from the start of Revlimid maintenance was 69 percent and decreased to 60 percent after two years. The overall survival rate was 93 percent after two years.
According to Dr. Minnema, these results were “not very promising” because they were similar to results of other studies in which patients received a donor stem cell transplant without maintenance therapy.
Eighty-seven percent of patients discontinued Revlimid therapy before completing all 24 cycles, mainly because of GVHD (43 percent), other severe side effects (17 percent), and disease progression (17 percent).
Of the 30 patients included in the study, 53 percent developed GVHD during Revlimid maintenance therapy. Thirty-seven percent developed acute GVHD, which occurs within the first 100 days after the transplant; 30 percent developed acute GVHD within the first two cycles of Revlimid maintenance.
According to the study authors, GVHD frequently develops in patients after they begin receiving reduced doses of immunosuppressive therapy. Patients in the study did not receive reduced doses of immunosuppressive therapy until after the first two cycles of Revlimid maintenance; however, patients frequently developed GVHD soon after starting Revlimid maintenance.
Based on these observations, the study authors attributed the rapid onset of GVHD to the Revlimid therapy itself.
“We think the immune-stimulatory effects of Revlimid are responsible for the induction of GVHD,” explained Dr. Minnema.
For more information, please see the study in the journal Blood (abstract).
Related Articles:
- ECT-001 Granted Regenerative Medicine Advanced Therapy (RMAT) Designation By U.S. FDA
- Number And Type Of Stem Cell Transplants Carried Out Each Year For Multiple Myeloma Vary Markedly Across U.S. Cancer Centers
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- 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
to me Stem Cell represent like a rope throw to you when you are in the water and can swim, of course te rope can breake and a lot of accident can occur, but the principle is the same,another way to get out of the water, even if it is for a short period of time more
keep it going
god bess you all
Carlos
Howard,
Thanks for this article. I just had an Allo transplant, so this is very informative for me. I am surprised that the patients were given 10 MG Revlimid before Day +100 and while still on Immunosuppressive drugs. I did find one very small European study that gave patients 5 MG or 10 MG of Revlimid after Day +100 and the patients that took 10 MG had a higher chance of developing GVHD. That group was next going to start a study of Revlimid maintenance after the patients were off Immunsosuppressive drugs and not showing cGVHD.
Any idea why the Doctors that ran this study would give Revlimid in the Day +60 range to patients? A Drug that can increase the chances of GVHD does not seem like a great idea that early after an Allo. I did a Full Allo, as opposed to a Mini. Any idea if that made any difference why the Doctors started these patients on Revlimid so soon after transplant?
Thanks again for all the great info that you provide.
Mark
Hi Mark,
Thank you for your comment, and sorry for this delayed reply. I contacted Dr. Minnema, the lead author of the study, about your questions. Her response is quoted below:
"I think it makes a difference that in the study we performed a mini-allo SCT opposed to al full allo-SCT. In the mini allo setting we do not see the GvHD problems in the first 100 days but in the time of lowering the immuno suppresive drugs. And since this takes 4 to 6 months it is much more logical to start early with the maintenance treatment when both immunosupprresive drugs are both present."
I found this to be very interesting. I'm on day 80 post Allo (full) and have been told that my levels are already increasing in the Myeloma. The way we are going to move ahead now is to start me on Revlimid, I haven't been told the dose yet until the new year. I already have slight GVHD and obviously the concern is the onset of severe GVHD, so they will be monitoring me very closely.
We don't know how effective the Revlimid will be or indeed if it will work, but from your article, it doesn't look that promising to me!
Sean
Hi Sean,
Sorry to hear that your myeloma hasn't responded as much as everyone might have hoped to your recent allo transplant.
You may want to lay out more of the details of your case in our discussion forum, since readers there (including the Beacon Medical Advisors) may have experience or advice that could be helpful.
I know there are at least one or two regular participants in the forum with a lot of knowledge about allo transplants.
There is also a discussion in the forum of donor lymphocyte infusions (DLIs) that may be helpful to you. Here is a link to it:
http://www.myelomabeacon.com/forum/donor-lymphocyte-infusions-dli-for-multiple-myeloma-t744.html
In addition, there was a presentation at the recent ASH meeting that discussed research into allo transplantation, DLIs, and related issues. You may learn a few things from the summary of the presentation in the forum,
http://www.myelomabeacon.com/forum/ash-2011-multiple-myeloma-discussion-day-2-t759.html#p3262
and it also may point you in the direction of other useful resources.
Best of luck,
Maike
Has anyone opted to go on a maintenance dose of drugs without having the stem cell transplant?? Am wondering too how long I can be on this prolonged regime of maintenance without significant side effects??
I have had a full response to the induction series of RVD.
Ken
Ken you ask if anyone had taken drugs with out the stem cell xplant - I came dowm with MM in 2004 and was treated with Thalidomide & Dex for 10 months then nothing No transplant or drugs of any kind however I have been taking Resveratol for about 4 years first at 200 mg daily then in 2010 at 250 mg I go in for blood tests every 4 months and they have been good however I notice that my oncologist is starting to monitor my urin out put more closely ?, I have been studying MM on several sites and have ask my oncologist about certain treatments I read about he told me "you may never need those treatments" I am currectly 73 years old and do have some residual problems I believe from the initial treatment.I know this is not exactly what you ask but thought you might have some interest in this info. N.G.
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