To Maintain Or Not To Maintain – That Is The Question!
Currently, there are three major controversies in multiple myeloma patient management: early versus late transplant, treat or observe ‘high-risk’ smoldering myeloma, and whether to use maintenance therapy. The latter is predominantly an issue following autologous stem cell transplantation.
In May, one of the world’s premier medical journals, the New England Journal of Medicine, published three articles about clinical trials comparing Revlimid (lenalidomide) maintenance versus observation. In two of the studies, Revlimid maintenance was given following autologous stem cell transplantation. In the third study, Revlimid maintenance was given following conventional therapy in patients not considered candidates for transplants. For all three studies, a computer selected which patients received Revlimid maintenance and which were only observed.
These articles are briefly summarized as follows:
- Dr. Michel Attal and his colleagues from the French Myeloma Group reported on 614 patients with a median follow up of 45 months. The median event-free survival (time to progressive disease) was 40 months in the Revlimid maintenance group versus 23 months for the observation group. However, there was no improvement in the overall survival of the patients (abstract).
- Dr. Philip McCarthy and his colleagues from the U.S. Intergroup reported on 460 patients with a median follow up of 34 months. The median event-free survival was 46 months in the Revlimid maintenance group versus 27 months in the observation group. With multiple analyses in a subgroup of patients, an overall survival benefit was observed (abstract).
- Dr. Antonio Palumbo from Italy, along with his colleagues, reported on 459 patients with a median follow up of 30 months. This study was a non-transplant study with three treatment groups: melphalan (Alkeran) plus prednisone; melphalan plus prednisone and Revlimid; and melphalan plus prednisone and Revlimid followed by Revlimid maintenance. They observed a median event-free survival of 13 months, 14 months, and 31 months, respectively. No improvement in survival was demonstrated at the time of the study analysis (abstract).
So, it appears there are three studies, all confirming the improvement in the time to progression, with one showing (in subgroup analysis) an improvement in survival.
Yet, there are disadvantages to maintenance therapy as well:
- Nine percent to 27 percent of the patients discontinued Revlimid maintenance due to side effects.
- The risk of developing a second cancer increased from 1 percent to 3 percent in the observation groups to 5 percent to 7 percent in the Revlimid maintenance groups.
- Only one study demonstrated an improvement in survival.
- It is unknown if re-treatment with the standard 25 mg dose of Revlimid will induce responses when the 10 mg dose used for maintenance is no longer effective (e.g. will the sub-therapeutic Revlimid dose drive the development of a resistant clone).
- Revlimid maintenance places a financial burden on society with a cost of approximately $165,000 per year.
- Finally, none of these studies included a quality of life assessment to gauge the patients’ perceptions of the consequences of chronic therapeutic administration of Revlimid.
Maintenance therapy with other anti-myeloma agents has also been reported.
Thalidomide (Thalomid) post-transplant has shown improved event-free survival in some studies. Unfortunately, long-term thalidomide use is associated with significant side effects, minimizing its potential use in this setting.
Preliminary data on Velcade (bortezomib) maintenance have been reported. After conventional therapy, Velcade appears to be effective as a maintenance therapy in combination with other agents. Velcade maintenance after autologous transplant also appears promising, but these trials are not yet mature enough to completely evaluate.
Given this controversy, the International Myeloma Working Group, an international group of over 150 myeloma experts, wrote, “Maintenance treatment can be associated with significant side effects, and none of the drugs evaluated is approved for maintenance therapy. Treatment decisions for individual patients must balance potential benefits and risks carefully, as a widely agreed-on standard is not established.”
Therefore, the question of “To maintain, or not to maintain?” has not clearly been answered. Each patient should discuss the aforementioned controversies with their treating physician before deriving a final decision.
For more information, see related Beacon news about the Revlimid maintenance studies and the IMWG consensus statement about maintenance therapy.
Dr. David H. Vesole is Co-Chief of the Myeloma Division and Director of Myeloma Research at The John Theurer Cancer Center at Hackensack University Medical Center. Dr. Vesole writes a quarterly column for The Myeloma Beacon.
Related Articles:
- Northern Lights: My First Six Weeks On Darzalex, Revlimid, And Dexamethasone
- A Northwest Lens On Myeloma: Anniversary And Decision Point
- A Northwest Lens On Myeloma: Treading Water
- Northern Lights: Trying To Make Plans In Advance
- Northern Lights: My History With Myeloma And How Things Have Changed Since My Diagnosis
Dr. Vesole. Thanks for a wonderful summary. I wish the results were different.
I have one question. You point out that quality of life was not included in the study. Too bad....but what is preventing us from conducting the study now? It would seem relatively simple to put together a key statistically satisfying questionnaire on QOL issues and circulate them among the surviving patients and all caregivers.
No drugs need be administered, randomization has been accomplished and memories of treatment are still fresh in the mind of the test subjects.
I believe many of us current patients who need to make decisions about maintenance could benefit from such important information.
I will even offer my statistical/patient background in developing and interpreting the QOL questionnaire. I would hope the IMF would provide the minimal financial support needed.
Whom do we contact
I agree with Gary. Very well laid-out. Now all we need are answers!
Each of us MM patients facing this decision need to come up with their own answer, given limited long term data. In my case, I feel the benefit of Revlimid maintenance far outweighs the risk, and have no side effects so far. My QOL is great! If I could, I would take pomalidomide instead, but that is not an option at this time. I am also on monthly IV Zometa, a biphosphanate that may have a positive prognostic effect as well. I hope that carfilzomib, pomalidomide, and especially elotuzumab will be available if and when the MM tiger rears its head again. in the meantime, enjoying life in the present is the key. Believing in my chosen therapy is important as well. Yes, it is expensive, but that is a cost that is well worth the benefit of a prolonged remission with a good QOL.
These studies are really different when comparing survival. Palumbo studiee was in NDMM patients 71 years or older, who all received melphan. Abstract shows lots of grade 3 toxicities in this group. So age or toxicities could decrease survival and may be more likely than maintenance not increasing survival.
The McCarthy study that showed survival was limited to patients under 65 &they did not receive 4 week cycles of melphalan like Palumbo pts. So maintenance is hard to compare between these studies.
If we do use these studies then the analysis says patients will not survive longer but the time they do live will be progression free. For cancer patients that provides better quality of life until they succomb to disease?
Perhaps maintenance does extend survival and we need more studies in NDMM Patients who are stem cell transplant naive and 65 years old or younger.
Given the ambiguous results of the maintenance studies, are there any patients out there who are going drug free or considering that alternative? I have just finished a course od Velcade with good results, and am pondering the next step. At 71, I want the best possible quality of life, and that means life with few or no side effects.
Madge,
I am caregiver to an mm patient, lambda. Dx 10/2011. She did four cycles of velcade-cyclo-dex and went into complete remission. Then double cytoxin before collecting stem cells. She did not do a sct. She is in stringent complete remission for 4 months now without further treatment. She has a brilliant quality of life off all drugs but biphosphanate. It's worth a try. Every month going drug free...is a miracle. If and when the disease returns the plan is to knock it down again with the velcade-cyclo-dex.
My father was diagnosed with MM in september 2008. He got a stem cell transplant (his own stem cells) in january 2010, in the summer of 2010 he had Velcade maintenance. He recently had his first relapse. His doctor is giving him velcade-cyclo-dex (2 times a week for 2 weeks, then 2 weeks free and then another round) He is in his third round now and is doing really well. He talked about saving the rest of his stem cells and doing a maintenance treatment this fall but now the head doctor is saying it is best to use them. I dont know who to ask but I´d really like to hear yours opinion if everyone would be so kind.
If the patients on maintenance are progression free of MM but do not survive longer, what are they dying from other than the blood dyscrasia?
Kidney disease? Pneumonia?
kristin
i am 73 years young. ihad my first stem cell tp. in 2003 andmy oncoligist saved my cells
when i had relapse in 2011 they gave me the saved cells for a 2nd transplant. i am also in a clinicl trial with geneticlly engeneered t-cells
unless he absolutly needs them now i would save them because so many new things are happening he may them in future for additional treatment
marty m
Please can someone explain to me about light chain numbers.
I was due to have my first stem cell transplant, but the doctors found the number of light chains to be 1500, this number means absolutely nothing to me, can anyone help please.
Kind regards.
Hi Neil, i think that some other patients have mentioned that you can get a whole series of free booklets from the International Myeloma Foundation....just go to their website. I recently did that and thus have the latest versions of the booklets...I had received others previously from conferences for patients and the cancer centre too. As someone pointed out recently, you can see these booklets online too...they are very informative.
Anyways, one of the booklets is called 'Understanding Serum Free Light Chain Assays'. Since Myeloma is a cancer of the plasma cells, which normally produce antibodies, we have to understand a bit about the normal function of plasma cells. Antibodies are actually composed of segments of proteins called immunoglobulins. There are both 'heavy' and 'light' varieties of immunoglobulins, and together they are assembled into antibodies. 'Free' light chains are ones that are free floating in the blood, not attached to antibody structures. Even in normal blood some light chains are floating, but in myeloma that number is dramatically increased! The serum light chain assay measures those proteins. Those proteins cause problems for us, since they are too light to be filtered out efficiently by the kidneys, and can cause kidney disease and other problems too.
Having said that much, I can't really comment on the numbers involved. Maybe someone else can elaborate on that for you......
Hello Kristin,
The Myeloma Beacon has a discussion and support forum where maintenance (and many other topics) are discussed on a regularly basis. Here is a link to the forum:
http://www.myelomabeacon.com/forum/
Also, this link will take you to discussions on the forum that are about maintenance therapy: http://bit.ly/PlwpMk .
Thank you 732719berk for your opinion. Yes that is my opinion as well. The doctors talk about the importance of the time without meds. - I am pretty new to this world.
I wanted to know if there is a message board where it would be better to discuss this, I would really appreciate it, seeing others opinion really helps. Thanks
Thank you very much for this