Hello,
I was diagnosed yesterday morning with high-risk smoldering multiple myeloma. My doctor wants me to enter a clinical trial of Revlimid, and I was wondering if anyone has any advice or experience regarding the trial.
Thank you.
Jacquie
Forums
-
Jacquieh - Name: Jacquie
- Who do you know with myeloma?: Smoldering Myeloma (myself)
- When were you/they diagnosed?: 07/12/2016
- Age at diagnosis: 46
Re: Revlimid trial for smoldering multiple myeloma
Hello Jacqui:
Treating smoldering multiple myeloma is a very new concept. There have been clinical trials started, but I am not aware of results that have been reported. High-risk smoldering multiple myeloma, however, I believe, means you have something like an 80% chance of turning active within two years. If you turn active, then your treatment would be 3 drugs in all likelihood (if you are in the States), which would be more invasive than Revlimid alone. In hindsight, my wife had MGUS for many years, but when she went to smoldering, she blasted through that in about a little more than a year. In our case, if this trial would have been available (it was not), and if we would have known better (we did not), it would have been the thing to do.
You could be lucky and dwell 10+ years at smoldering, but you do not know that for sure. The idea of the trial is to establish whether or not, over a population, this will be successful at suppressing the multiple myeloma. The trials that I have read on this topic were randomized, so ask your doctor about that, it may be that if you enroll, that you have a 50% chance of being in the Revlimid arm, or else nothing (the present day standard of care for today).
Strictly my guess, and not to be relied on, I think that it will turn out that giving Rev to high-risk smoldering multiple myeloma will turn out to be better, in the sense that at the cost of some side effects near term, the time to progression of full blown multiple myeloma will be extended significantly. That is only my guess. By the time the data is actually in, that will be too late for your decision (however, in your case, I do not think you need to decide tomorrow, and maybe in a year, the trial might still be available).
So please do your research, and good luck to you. I would like to advise you, however, that there are also trials using Darzalex (daratumumab) for high-risk smoldering multiple myeloma. Darzalex is a monoclonal antibody. The monoclonal antibodies, at present, are believed to have side effects that go away completely over time. For Revlimid, if you stop taking them, the side effects usually subside, but may last long term. For that reason, some believe that monoclonal antibodies may be better in your case. However, that clinical trial may not be available in your center.
Good luck to you in your decision making.
Treating smoldering multiple myeloma is a very new concept. There have been clinical trials started, but I am not aware of results that have been reported. High-risk smoldering multiple myeloma, however, I believe, means you have something like an 80% chance of turning active within two years. If you turn active, then your treatment would be 3 drugs in all likelihood (if you are in the States), which would be more invasive than Revlimid alone. In hindsight, my wife had MGUS for many years, but when she went to smoldering, she blasted through that in about a little more than a year. In our case, if this trial would have been available (it was not), and if we would have known better (we did not), it would have been the thing to do.
You could be lucky and dwell 10+ years at smoldering, but you do not know that for sure. The idea of the trial is to establish whether or not, over a population, this will be successful at suppressing the multiple myeloma. The trials that I have read on this topic were randomized, so ask your doctor about that, it may be that if you enroll, that you have a 50% chance of being in the Revlimid arm, or else nothing (the present day standard of care for today).
Strictly my guess, and not to be relied on, I think that it will turn out that giving Rev to high-risk smoldering multiple myeloma will turn out to be better, in the sense that at the cost of some side effects near term, the time to progression of full blown multiple myeloma will be extended significantly. That is only my guess. By the time the data is actually in, that will be too late for your decision (however, in your case, I do not think you need to decide tomorrow, and maybe in a year, the trial might still be available).
So please do your research, and good luck to you. I would like to advise you, however, that there are also trials using Darzalex (daratumumab) for high-risk smoldering multiple myeloma. Darzalex is a monoclonal antibody. The monoclonal antibodies, at present, are believed to have side effects that go away completely over time. For Revlimid, if you stop taking them, the side effects usually subside, but may last long term. For that reason, some believe that monoclonal antibodies may be better in your case. However, that clinical trial may not be available in your center.
Good luck to you in your decision making.
-
JPC - Name: JPC
Re: Revlimid trial for smoldering multiple myeloma
Welcome to the forum, Jacquie. Sorry to hear about your diagnosis, but you've come to a great place for information and support.
Before I give any feedback about the trial you're considering, I think it's important to ask what reasons there are for your doctor having classified you as having high-risk smoldering multiple myeloma. What are your key lab values, such as your M-spike, free light chain levels and ratio, bone marrow plasma cell percentage, and chromosomal abnormalities?
On the issue of treating smoldering myeloma, like many things with this disease, there really isn't anything new. Myeloma specialists have been investigating whether or not to treat smoldering multiple myeloma since at least the early 1990s.
Up until about 5 years ago, the results of the clinical trials that have investigated early treatment of smoldering myeloma usually have been that there is no overall survival benefit to early treatment. Check the background section of this presentation:
Mateos, M.V., "Should We Treat Smoldering Multiple Myeloma Patients?"
for some of the studies that have been done in the past on this topic.
Three years ago, however, Spanish researchers published results of a trial testing Revlimid and dexamethasone in high-risk smoldering myeloma patients. They found that early treatment provided an overall survival benefit. You can find some discussion of those results in these articles:
"Revlimid Plus Dexamethasone Delays Progression And Extends Survival In High-Risk Smoldering Myeloma," The Myeloma Beacon, August 2, 2013
"Smoldering Myeloma: What Do The Latest Research Findings Mean? A Discussion With Dr. Ola Landgren," The Myeloma Beacon, January 13, 2012
The Spanish researchers also just recently published updated results from their trial. From the abstract, it appears that there is still an overall survival benefit to early treatment with Revlimid and dex, but it is not clear whether the benefit is statistically significant.
Mateos, M.V., et al., "Lenalidomide plus dexamethasone versus observation in patients with high-risk smoldering multiple myeloma (QuiRedex): long-term follow-up a randomised, controlled, phase 3 trial," The Lancet Oncology, July 2016 (abstract)
Note that the Spanish study does not make the sort of apples-to-apples comparison you really would like to see – the sort of apples-to-apples comparison that was usually investigated in older trials.
In the previous trials that were very carefully designed, the comparison was always between
1. Early treatment of smoldering myeloma with some treatment regimen, and
2. Treatment at progression ("delayed treatment") WITH THE SAME TREATMENT REGIMEN.
The Spanish study was different. Early treatment was with Revlimid and dex. But the delayed treatment regimen was not specified. It was left open to the patient's doctor and the patient. However, in Spain, this meant that most of the patients who got delayed treatment almost certainly were treated with a regimen that did NOT include Revlimid, since Revlimid was not used in newly diagnosed patients in Spain in routine practice.
Bottom line:
Treating high-risk smoldering myeloma will almost certainly delay a patient's progression to symptomatic multiple myeloma. This will be true whether the treatment is with Revlimid, Velcade, Darzalex, or any other myeloma therapy.
Whether or not a patient's overall survival will be improved by early treatment is still somewhat of an open question.
Before I give any feedback about the trial you're considering, I think it's important to ask what reasons there are for your doctor having classified you as having high-risk smoldering multiple myeloma. What are your key lab values, such as your M-spike, free light chain levels and ratio, bone marrow plasma cell percentage, and chromosomal abnormalities?
On the issue of treating smoldering myeloma, like many things with this disease, there really isn't anything new. Myeloma specialists have been investigating whether or not to treat smoldering multiple myeloma since at least the early 1990s.
Up until about 5 years ago, the results of the clinical trials that have investigated early treatment of smoldering myeloma usually have been that there is no overall survival benefit to early treatment. Check the background section of this presentation:
Mateos, M.V., "Should We Treat Smoldering Multiple Myeloma Patients?"
for some of the studies that have been done in the past on this topic.
Three years ago, however, Spanish researchers published results of a trial testing Revlimid and dexamethasone in high-risk smoldering myeloma patients. They found that early treatment provided an overall survival benefit. You can find some discussion of those results in these articles:
"Revlimid Plus Dexamethasone Delays Progression And Extends Survival In High-Risk Smoldering Myeloma," The Myeloma Beacon, August 2, 2013
"Smoldering Myeloma: What Do The Latest Research Findings Mean? A Discussion With Dr. Ola Landgren," The Myeloma Beacon, January 13, 2012
The Spanish researchers also just recently published updated results from their trial. From the abstract, it appears that there is still an overall survival benefit to early treatment with Revlimid and dex, but it is not clear whether the benefit is statistically significant.
Mateos, M.V., et al., "Lenalidomide plus dexamethasone versus observation in patients with high-risk smoldering multiple myeloma (QuiRedex): long-term follow-up a randomised, controlled, phase 3 trial," The Lancet Oncology, July 2016 (abstract)
Note that the Spanish study does not make the sort of apples-to-apples comparison you really would like to see – the sort of apples-to-apples comparison that was usually investigated in older trials.
In the previous trials that were very carefully designed, the comparison was always between
1. Early treatment of smoldering myeloma with some treatment regimen, and
2. Treatment at progression ("delayed treatment") WITH THE SAME TREATMENT REGIMEN.
The Spanish study was different. Early treatment was with Revlimid and dex. But the delayed treatment regimen was not specified. It was left open to the patient's doctor and the patient. However, in Spain, this meant that most of the patients who got delayed treatment almost certainly were treated with a regimen that did NOT include Revlimid, since Revlimid was not used in newly diagnosed patients in Spain in routine practice.
Bottom line:
Treating high-risk smoldering myeloma will almost certainly delay a patient's progression to symptomatic multiple myeloma. This will be true whether the treatment is with Revlimid, Velcade, Darzalex, or any other myeloma therapy.
Whether or not a patient's overall survival will be improved by early treatment is still somewhat of an open question.
-
JimNY
Re: Revlimid trial for smoldering multiple myeloma
Good morning:
To JimNY, you always (not usually, but always) give us very good and informative posts, I had not seen those references before for Dr. Mateos, so thank you very much. I wanted to add the following comments, however. The International Myeloma Working Group (IWMG) updated the definition of active multiple myeloma and smoldering multiple myeloma last year. There were definitions before for active multiple myeloma and smoldering multiple myeloma, but I do not think there was a hard definition before last year for high-risk smoldering multiple. However, I think that for the first time, that term received a "hard" definition according to published IMWG standards. Before last year, the term was used (as you showed in your links), but the term was perhaps used differently by different doctors and in different studies.
If I am saying anything inaccurate here, I would be very grateful if someone could provide additional insight so that I and others can have a better understanding of the issue.
I would guess that the study you pointed out by Dr. Mateos was very likely an input into the updated definitions (Dr. Mateos is an active member of the IMWG). One result of the updated definition was the re-classification of some of the "ultra" high risk smoldering multiple myeloma patients to active multiple myeloma, under the so called "Slim-CRAB" criteria. This is of interest to me, in that when my wife was classified as smoldering in 2013, it was accurate according to accepted criteria at that time. However, she would have met one of the "Slim" criteria, and would have been slotted for active treatment somewhat earlier.
The main issue with the "Slim" criteria, I understand, is as follows. Doctors were tracking smoldering multiple myeloma and even though they were being monitored, some patients were getting bad organ or bone damage. The idea was to stop that from happening. In my wife's case, the bad effect was not organ or bone damage, but bad anemia, which, thank God, mostly recovered from treatment, though still on the low side.
The IWMG also has a new definition for high risk smoldering multiple myeloma last year. Remember, the ultra high risk has already been peeled off. The definition of high risk smoldering myeloma now includes some of the cytogenetic abnormalities, such as t 4,14.
Since the high risk smoldering myeloma category is newly defined, newer studies are being designed to specifically address that category, as to whether or not it is beneficial to treat it. As JimNY points out, the questions are open, which is why they need to do the clinical trials to answer the questions.
For our personal situation, the ship has sailed, and it is no longer relevant to us, but I can state that potentially bad things could have occurred to patients being actively monitored with smoldering multiple myeloma (under the old definitions), so it is of interest to me.
So Jacqui, JimNY raises a good point. Make sure that your doctor is a myeloma specialist, and is on top of the latest changes in the state of the art of multiple myeloma practice. Research the clinical trial extensively, and go forward with it only if you are comfortable with it. Good luck.
To JimNY, you always (not usually, but always) give us very good and informative posts, I had not seen those references before for Dr. Mateos, so thank you very much. I wanted to add the following comments, however. The International Myeloma Working Group (IWMG) updated the definition of active multiple myeloma and smoldering multiple myeloma last year. There were definitions before for active multiple myeloma and smoldering multiple myeloma, but I do not think there was a hard definition before last year for high-risk smoldering multiple. However, I think that for the first time, that term received a "hard" definition according to published IMWG standards. Before last year, the term was used (as you showed in your links), but the term was perhaps used differently by different doctors and in different studies.
If I am saying anything inaccurate here, I would be very grateful if someone could provide additional insight so that I and others can have a better understanding of the issue.
I would guess that the study you pointed out by Dr. Mateos was very likely an input into the updated definitions (Dr. Mateos is an active member of the IMWG). One result of the updated definition was the re-classification of some of the "ultra" high risk smoldering multiple myeloma patients to active multiple myeloma, under the so called "Slim-CRAB" criteria. This is of interest to me, in that when my wife was classified as smoldering in 2013, it was accurate according to accepted criteria at that time. However, she would have met one of the "Slim" criteria, and would have been slotted for active treatment somewhat earlier.
The main issue with the "Slim" criteria, I understand, is as follows. Doctors were tracking smoldering multiple myeloma and even though they were being monitored, some patients were getting bad organ or bone damage. The idea was to stop that from happening. In my wife's case, the bad effect was not organ or bone damage, but bad anemia, which, thank God, mostly recovered from treatment, though still on the low side.
The IWMG also has a new definition for high risk smoldering multiple myeloma last year. Remember, the ultra high risk has already been peeled off. The definition of high risk smoldering myeloma now includes some of the cytogenetic abnormalities, such as t 4,14.
Since the high risk smoldering myeloma category is newly defined, newer studies are being designed to specifically address that category, as to whether or not it is beneficial to treat it. As JimNY points out, the questions are open, which is why they need to do the clinical trials to answer the questions.
For our personal situation, the ship has sailed, and it is no longer relevant to us, but I can state that potentially bad things could have occurred to patients being actively monitored with smoldering multiple myeloma (under the old definitions), so it is of interest to me.
So Jacqui, JimNY raises a good point. Make sure that your doctor is a myeloma specialist, and is on top of the latest changes in the state of the art of multiple myeloma practice. Research the clinical trial extensively, and go forward with it only if you are comfortable with it. Good luck.
-
JPC - Name: JPC
Re: Revlimid trial for smoldering multiple myeloma
I was diagnosed about a month ago with a myeloma that has the t(4;14) translocation. I start treatment in a few days even though I do not meet the CRAB criteria. My calcium levels are fine and my skeletal x-rays showed no sign of bone damage due to myeloma.
However, I have anemia; it started many years prior to my myeloma diagnosis. Around the time my anemia started, I developed a lymphoproliferative disorder that has only recently been given a name, hairy cell leukemia. Because I am already anemic, my hemoglobin level is not a good indicator for start of treatment of my myeloma.
I have a similar problem with my kidney function, which is already impaired due to a side effect from a medicine that I’ve been taking to ward off iron overload. The iron overload is caused by all the blood transfusions I’ve received.
Because of these factors, my hematologist thought it best to proceed with treatment.
I gave the hematologist's advice some thought and decided that it is better to treat my myeloma now than run the risk of not detecting the start of a more active phase of my myeloma.
My treatment is to use the chemo combination called CyBorD (cyclophosphamide, Velcade, and dexamethasone), which has no Revlimid component. This is because Revlimid is not as good as Velcade (bortezomib) in treating those myelomas with the t(4;14) translocation.
Good luck to you Jacquleh. At least you now know that others have jumped the gun in the treatment phase.
However, I have anemia; it started many years prior to my myeloma diagnosis. Around the time my anemia started, I developed a lymphoproliferative disorder that has only recently been given a name, hairy cell leukemia. Because I am already anemic, my hemoglobin level is not a good indicator for start of treatment of my myeloma.
I have a similar problem with my kidney function, which is already impaired due to a side effect from a medicine that I’ve been taking to ward off iron overload. The iron overload is caused by all the blood transfusions I’ve received.
Because of these factors, my hematologist thought it best to proceed with treatment.
I gave the hematologist's advice some thought and decided that it is better to treat my myeloma now than run the risk of not detecting the start of a more active phase of my myeloma.
My treatment is to use the chemo combination called CyBorD (cyclophosphamide, Velcade, and dexamethasone), which has no Revlimid component. This is because Revlimid is not as good as Velcade (bortezomib) in treating those myelomas with the t(4;14) translocation.
Good luck to you Jacquleh. At least you now know that others have jumped the gun in the treatment phase.
-
Wobbles - Name: Joe
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: June 2016
- Age at diagnosis: 67
Re: Revlimid trial for smoldering multiple myeloma
Hello, Jackie:
Can you advise what is the treatment regimen that they are proposing for the clinical trial that has been offered to you?
Regards,
Can you advise what is the treatment regimen that they are proposing for the clinical trial that has been offered to you?
Regards,
-
JPC - Name: JPC
Re: Revlimid trial for smoldering multiple myeloma
Hello JCP,
Treatment regimen: 25 mg of Revlimid, with a second bone biopsy in three months. My follow-up appointments /blood draws will be every month.
Huge thanks to you, JimNY, and Wobbles. I appreciate all of the information you provided.
Regards,
Jacquie
Treatment regimen: 25 mg of Revlimid, with a second bone biopsy in three months. My follow-up appointments /blood draws will be every month.
Huge thanks to you, JimNY, and Wobbles. I appreciate all of the information you provided.
Regards,
Jacquie
-
Jacquieh - Name: Jacquie
- Who do you know with myeloma?: Smoldering Myeloma (myself)
- When were you/they diagnosed?: 07/12/2016
- Age at diagnosis: 46
Re: Revlimid trial for smoldering multiple myeloma
Hello Jaquie:
After some thought, I think that JimNY has a point in that Revlimid has been tried on smoldering multiple myeloma for quite some time, and there have been results reported along the lines of what Jim described. If you are high risk (under the new definition), and believe you may have relatively quick progression, based on the data, it might appeal to you to hold it off some time with Revlimid.
I had heard, however, that there are newer trials with different agents, that might achieve better results. The trial available to you may be the one that is offered at your center, and you may not have access to some others. However, here is a link to information about a clinical trial testing Darzalex in smoldering myeloma:
"A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma"
I would think using the better more modern agents would have the potential to have better results than the Revlimid trials, in general. It's a clinical trial, so you would need to be comfortable with it. Revlimid (and Darzalex) each as a single agent do have side effects. However, they can be considered "safe" for a healthy person. I would suggest that you ask whether there any other trials available, other than the Revlimid trial. My understanding is that right now, the only treatment options for smoldering, if you are interested, is on a clinical trial.
After some thought, I think that JimNY has a point in that Revlimid has been tried on smoldering multiple myeloma for quite some time, and there have been results reported along the lines of what Jim described. If you are high risk (under the new definition), and believe you may have relatively quick progression, based on the data, it might appeal to you to hold it off some time with Revlimid.
I had heard, however, that there are newer trials with different agents, that might achieve better results. The trial available to you may be the one that is offered at your center, and you may not have access to some others. However, here is a link to information about a clinical trial testing Darzalex in smoldering myeloma:
"A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma"
I would think using the better more modern agents would have the potential to have better results than the Revlimid trials, in general. It's a clinical trial, so you would need to be comfortable with it. Revlimid (and Darzalex) each as a single agent do have side effects. However, they can be considered "safe" for a healthy person. I would suggest that you ask whether there any other trials available, other than the Revlimid trial. My understanding is that right now, the only treatment options for smoldering, if you are interested, is on a clinical trial.
-
JPC - Name: JPC
Re: Revlimid trial for smoldering multiple myeloma
JPC,
Thank you so much for the additional information. I meet with my oncologist in a few weeks and will discuss Revlimid with Darzalex. The level of information when first diagnosed can feel overwhelming. I appreciate all the help I can get. (:
Jacquie
Thank you so much for the additional information. I meet with my oncologist in a few weeks and will discuss Revlimid with Darzalex. The level of information when first diagnosed can feel overwhelming. I appreciate all the help I can get. (:
Jacquie
-
Jacquieh - Name: Jacquie
- Who do you know with myeloma?: Smoldering Myeloma (myself)
- When were you/they diagnosed?: 07/12/2016
- Age at diagnosis: 46
Re: Revlimid trial for smoldering multiple myeloma
Good luck, Jacquie. It is hard to try and get all of the information you need to make a decision, particularly when this is new to you, but eventually you "learn the ropes". As I believe you understand, I am not recommending anything specific, that is for you to decide what you are comfortable with, but I am trying to inform you with respect to possible other options. Good luck.
-
JPC - Name: JPC
15 posts
• Page 1 of 2 • 1, 2