This is a great thread.
My oncologist, like Mikeb's, tells me that he considers multiple myeloma a chronic illness and that I will die of something else. While I kind of like this characterization, I do feel that the "something else" may not be myeloma, but something related to it or its treatment, such as kidney failure, or a heart problem or an infection,
However, having said that, Mikeb is definitely right about defining the parameters of the term 'cure." It hasn't been defined, as of yet. In the old days, you were considered "cured" of any cancer if you survived without recurrence for 5 years. I don't think that definition would be satisfactory today.
Forums
Re: Progress toward a multiple myeloma cure?
Just read this thread. Very interesting. Having had a auto three years ago I witnessed the real exposure to allo transplants. Seven paitients died during my six week time at the transplant center. The risk of death is real and should not be taken lightly. However, if statistically you could be cured (no treatment for 10 years) it might be worth the gamble. These chemo drugs and their long term side effects impact quality of life and will likely lead to our death prior to 10 years of treatment.
Just my two cents! Jerry
Just my two cents! Jerry
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JBarnes - Name: Jerry Barnes
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: Aug 17, 2012
- Age at diagnosis: 54
Re: Progress toward a multiple myeloma cure?
The landscape is constantly changing. Four new drugs have been approved this past year and two of them, Darzalex (daratumumab) and Empliciti (elotuzumab) are monoclonal antibodies (immune system boosters). I am especially impressed with the early tests with Darzalex and think is can be game changer. Not curative, but in combination with other novel agents, has the real possibility of turning multiple myeloma into a long term chronic but controllable form of cancer. If you can control multiple myeloma with the drugs and assuming that they are well tolerated, than that will likely be the direction that almost all doctors and patients will opt for. The use of the more aggressive treatments will be reduced to those patients that do not respond to these new drugs or have some especially aggressive form of cancer. I fully expect even more of these immune system type drugs to be approved in the next few years.
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: Progress toward a multiple myeloma cure?
Just to throw in, when I was recently at Dana Farber talking with Dr. John Koreth, one of the allo transplant doctors there, I specifically asked him how "success" or "cure" was defined. He said it was >10 year progression free, chemo-free period. Keep in mind, this is without chemo, which is huge. After those ten (or hopefully more) years, you still have the option of all the sequential chemotherapy ahead of you.
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Tracy J - Name: Tracy Jalbuena
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: 2014
- Age at diagnosis: 42
Re: Progress toward a multiple myeloma cure?
Good morning, Tracy:
Thank you for your post. It raises a question. I had previously read in the literature that post allo, if you went 5 years without a remission, that very likely the myeloma would never recur.
Based on your comment that you relayed from Dr. Koreth, it seemed as if he is possibly aware of instances of relapse between 5 and 10 years. As a physician yourself, can you please share your opinion on this? Am I reading this correctly, 5 years is not good enough??
Thanks and regards
Thank you for your post. It raises a question. I had previously read in the literature that post allo, if you went 5 years without a remission, that very likely the myeloma would never recur.
Based on your comment that you relayed from Dr. Koreth, it seemed as if he is possibly aware of instances of relapse between 5 and 10 years. As a physician yourself, can you please share your opinion on this? Am I reading this correctly, 5 years is not good enough??
Thanks and regards
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JPC - Name: JPC
Re: Progress toward a multiple myeloma cure?
Thanks everybody for contributing the interesting posts.
A couple of points I would like to make. Great discussion by MikeB and Ellen with regard to not having a definition for cure in myeloma. My read of the literature suggests we are far behind other blood cancers with respect to defining cure is that, unfortunately, we are behind with using MRD (molecular) testing, so few myeloma patients stay in remission long term without therapy, and that cure is not the goal for most myeloma patients therapy.
In my opinion, time and testing are the two most important factors for determining cure, with time in a drug free remission being the most important. I do agree with Ellen that likely 5 years of drug free remission is not enough time to think a standard risk myeloma patient is cured. The studies with longer term follow up seem to suggest 10 years or so is more like it for myeloma. I got to be friendly with one of the Fellows where I am being treated and he suggested that as a "rule of thumb", if a patient can go 3 times longer in remission without detectable disease or any therapy than was expected at the outset, that the patient may be cured. We were discussing allo transplant at the time which is a known cure for various blood cancers. Of course that brings up the issue of how accurate the doctors/testing is to get that estimate. For that reason high risk patients have an idea if they may be cured before a standard risk patient. Note the study that Mr. Potatohead posted with regard to Total Therapy. It is thought the high risk patients may be cured after 5 years while the standard risk patients may be cured after 10.
Interesting post by Mr. Potatohead. We discussed that paper in the forum here.
"Latest Total Therapy long-term survival results" (started Oct 9, 2014)
As I have mentioned here before, Total Therapy is not for me since I am a believer in immunotherapy/healthy functioning donor immune system as opposed to long cycles of drugs, but I am curious about something. If there was a test that could prove total therapy was a cure, what percentage of patients would it have to cure for patients to consider doing it? My understanding is that total therapy takes about 4 years to complete - 2 rounds of VTD-PACE, 2 autos, 2 more rounds of VTD-PACE followed by 3 years of RVD maintenance.
Hopefully some patients would answer that as I am curious what percentage chance a patient would want to have of never relapsing to do something like Total Therapy.
A couple of points I would like to make. Great discussion by MikeB and Ellen with regard to not having a definition for cure in myeloma. My read of the literature suggests we are far behind other blood cancers with respect to defining cure is that, unfortunately, we are behind with using MRD (molecular) testing, so few myeloma patients stay in remission long term without therapy, and that cure is not the goal for most myeloma patients therapy.
In my opinion, time and testing are the two most important factors for determining cure, with time in a drug free remission being the most important. I do agree with Ellen that likely 5 years of drug free remission is not enough time to think a standard risk myeloma patient is cured. The studies with longer term follow up seem to suggest 10 years or so is more like it for myeloma. I got to be friendly with one of the Fellows where I am being treated and he suggested that as a "rule of thumb", if a patient can go 3 times longer in remission without detectable disease or any therapy than was expected at the outset, that the patient may be cured. We were discussing allo transplant at the time which is a known cure for various blood cancers. Of course that brings up the issue of how accurate the doctors/testing is to get that estimate. For that reason high risk patients have an idea if they may be cured before a standard risk patient. Note the study that Mr. Potatohead posted with regard to Total Therapy. It is thought the high risk patients may be cured after 5 years while the standard risk patients may be cured after 10.
Interesting post by Mr. Potatohead. We discussed that paper in the forum here.
"Latest Total Therapy long-term survival results" (started Oct 9, 2014)
As I have mentioned here before, Total Therapy is not for me since I am a believer in immunotherapy/healthy functioning donor immune system as opposed to long cycles of drugs, but I am curious about something. If there was a test that could prove total therapy was a cure, what percentage of patients would it have to cure for patients to consider doing it? My understanding is that total therapy takes about 4 years to complete - 2 rounds of VTD-PACE, 2 autos, 2 more rounds of VTD-PACE followed by 3 years of RVD maintenance.
Hopefully some patients would answer that as I am curious what percentage chance a patient would want to have of never relapsing to do something like Total Therapy.
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Mark11
Re: Progress toward a multiple myeloma cure?
I read an interesting article:
"Is this the cure for cancer? Genetically modified blood turned into 'living drug' in stunning new therapy that hunts down and destroys diseased cells and prevents them from returning - possibly FOREVER", Daily Mail, Feb 16, 2016 (full text of article)
It reports about the advances being made in T-cell immunotherapy in the treatment of 'liquid' cancers like leukemia etc.
I wonder whether myeloma – also being a 'liquid' cancer – will see benefits as well.
Robin
"Is this the cure for cancer? Genetically modified blood turned into 'living drug' in stunning new therapy that hunts down and destroys diseased cells and prevents them from returning - possibly FOREVER", Daily Mail, Feb 16, 2016 (full text of article)
It reports about the advances being made in T-cell immunotherapy in the treatment of 'liquid' cancers like leukemia etc.
I wonder whether myeloma – also being a 'liquid' cancer – will see benefits as well.
Robin
Re: Progress toward a multiple myeloma cure?
Mark11 wrote:
That is a really tough question, Mark, and one that I don't know I'm capable of answering without actually being in the situation. Like you, I wasn't all that interested in Total Therapy. When I looked at the options I had and the potential for long-term remission just with them, I decided that a four-year period with my quality of life being hugely impacted was something I didn't want to risk. (That's just me and I realize that this is not the right decision for a lot of other people.) With all of the new treatments on the horizon and (particularly for the immunotherapies) their potential to cure the disease, it would take a lot of certainty that I would be absolutely cured in order for me to want to go through that four year process and the toll it would take on my body. Nonetheless, I might go with it if I were faced with the decision. I just don't know.
As I have mentioned here before, Total Therapy is not for me since I am a believer in immunotherapy/healthy functioning donor immune system as opposed to long cycles of drugs, but I am curious about something. If there was a test that could prove total therapy was a cure, what percentage of patients would it have to cure for patients to consider doing it? My understanding is that total therapy takes about 4 years to complete - 2 rounds of VTD-PACE, 2 autos, 2 more rounds of VTD-PACE followed by 3 years of RVD maintenance.
Hopefully some patients would answer that as I am curious what percentage chance a patient would want to have of never relapsing to do something like Total Therapy.
That is a really tough question, Mark, and one that I don't know I'm capable of answering without actually being in the situation. Like you, I wasn't all that interested in Total Therapy. When I looked at the options I had and the potential for long-term remission just with them, I decided that a four-year period with my quality of life being hugely impacted was something I didn't want to risk. (That's just me and I realize that this is not the right decision for a lot of other people.) With all of the new treatments on the horizon and (particularly for the immunotherapies) their potential to cure the disease, it would take a lot of certainty that I would be absolutely cured in order for me to want to go through that four year process and the toll it would take on my body. Nonetheless, I might go with it if I were faced with the decision. I just don't know.
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Mike F - Name: Mike F
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: May 18, 2012
- Age at diagnosis: 53
Re: Progress toward a multiple myeloma cure?
Like MikeF I am disappointed we go no takers on that question.
I saw a paper that was written as commentary on a small study (92 patients) I have posted before due to the high overall survival (62% at 10 years) of the patients. The study itself I have not seen the full text of because it still requires payment.
Here is the abstract of the study.
"Despite survival improvement with novel agents and use of autologous hematopoietic stem cell transplantation (HSCT), cure of patients with multiple myeloma remains anecdotal. Initial observations suggested that chronic GvHD was accompanied by an anti-myeloma effect after myeloablative HSCT, but unfortunately this procedure was hampered by high non-relapse mortality (NRM). To maximize the anti-myeloma effect and minimize NRM, we developed a non-myeloablative (NMA) regimen associated with a high incidence of chronic GvHD and tested its efficacy on patient survival and disease eradication. From 2001 to 2010, 92 patients aged⩽65 years with a compatible sibling donor received autologous HSCT followed by an outpatient NMA allogeneic HSCT using a conditioning of fludarabine and cyclophosphamide. Patient median age was 52 years and 97% presented Durie-Salmon stages II-III disease. After a median follow-up of 8.8 years, probability of 10-year progression free and overall survival were 41% and 62%, respectively. Although the cumulative incidence of extensive chronic GvHD was high (at 79%), the majority of long-term survivors were off immunosuppressive drugs by year 5 and NRM was low (at 10%). Together, our results suggest that potential multiple myeloma cure can be achieved with NMA transplantation regimens that maximize graft-versus-myeloma effect and minimize NRM."
Reference:
I Ahmad et al, "Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation", Bone Marrow Transplantation, December 2015 (abstract)
I agree with pretty much everything in this commentary and I want to highlight two of Dr. Bruno's comments which I have made in different ways in the past.
"All these studies were, however, designed well before potent anti-myeloma agents such as bortezomib, carfilzomib or lenalidomade and pomalidomide became readily available. Although the annual reports of the European Society of Blood and Marrow Transplantation show an important transplant activity in plasma cell disorders in recent years, the real role of the combination of new drugs with graft-versus-myeloma has never been fully explored in this incurable disease. This may partly be attributed to the current limited interest on cell therapy strategies in myeloma. New drugs and graft-versus-myeloma are not mutually exclusive, and their synergy has clearly been shown in relapsed patients."
Those last 2 sentences are points I have made many times here in the Forum.
This is a long paragraph but I have to copy it all to appreciate the last sentence.
"Depth of response is another key factor to predict clinical outcomes in myeloma. Thanks to advanced molecular technology, PCR-based minimal residual disease (MRD) detection currently represents a powerful outcome predictor. In the GIMEMA-VEL-03-096 trial, 39 patients who received consolidation with a combination bortezomib-thalidomide-dexamethasone (VTD) after an autograft were monitored for MRD by qualitative nested-PCR and quantitative PCR (qPCR). After a median follow-up of 8 years, overall survival was 72% for patients in major MRD response versus 48% for those with MRD persistence (P=0.041).17 This was a hallmark study that clearly showed that molecular remissions could be obtained with new drug-based consolidation treatments. However, the same group recently reported on the long-term outcomes of molecular monitoring after a tandem ‘auto-non-myeloablative allo’ approach.18 Twenty-six patients were prospectively evaluated by both nested-PCR and qPCR. Specific markers were generated in 19/26. At the median follow-up of 12.1, overall survival for the whole-patient cohort was not reached and event-free survival was 4 years from the allograft. Rate of nested-PCR negativity increased up to 47% at 1 year after the allograft, whereas the molecular response rate was 63% at 2 years by qPCR. At a remarkable median follow-up of 12.1, median overall survival and event-free survival were not reached in patients who achieved nested-PCR negativity while they were 3.3 and 1.5 years, respectively, in the remaining patients. Graft-versus-myeloma appeared to determine prolonged molecular remission rates, higher than those reported after autografting and VTD. Although the number of patients studied was small, one may provocatively infer that, had these findings been obtained with other treatment modalities, they would have been emphasized more in the scientific community."
I could not agree with that last sentence any more:
"Although the number of patients studied was small, one may provocatively infer that, had these findings been obtained with other treatment modalities, they would have been emphasized more in the scientific community."
Source:
B Bruno, "Allogeneic transplantation for multiple myeloma: yes, no or maybe?," Bone Marrow Transplantation, Feb 22, 2016 (full text of article)
Could you imagine how much press there would be if a new form of immunotherapy could show long term remissions like that?
Mark
I saw a paper that was written as commentary on a small study (92 patients) I have posted before due to the high overall survival (62% at 10 years) of the patients. The study itself I have not seen the full text of because it still requires payment.
Here is the abstract of the study.
"Despite survival improvement with novel agents and use of autologous hematopoietic stem cell transplantation (HSCT), cure of patients with multiple myeloma remains anecdotal. Initial observations suggested that chronic GvHD was accompanied by an anti-myeloma effect after myeloablative HSCT, but unfortunately this procedure was hampered by high non-relapse mortality (NRM). To maximize the anti-myeloma effect and minimize NRM, we developed a non-myeloablative (NMA) regimen associated with a high incidence of chronic GvHD and tested its efficacy on patient survival and disease eradication. From 2001 to 2010, 92 patients aged⩽65 years with a compatible sibling donor received autologous HSCT followed by an outpatient NMA allogeneic HSCT using a conditioning of fludarabine and cyclophosphamide. Patient median age was 52 years and 97% presented Durie-Salmon stages II-III disease. After a median follow-up of 8.8 years, probability of 10-year progression free and overall survival were 41% and 62%, respectively. Although the cumulative incidence of extensive chronic GvHD was high (at 79%), the majority of long-term survivors were off immunosuppressive drugs by year 5 and NRM was low (at 10%). Together, our results suggest that potential multiple myeloma cure can be achieved with NMA transplantation regimens that maximize graft-versus-myeloma effect and minimize NRM."
Reference:
I Ahmad et al, "Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation", Bone Marrow Transplantation, December 2015 (abstract)
I agree with pretty much everything in this commentary and I want to highlight two of Dr. Bruno's comments which I have made in different ways in the past.
"All these studies were, however, designed well before potent anti-myeloma agents such as bortezomib, carfilzomib or lenalidomade and pomalidomide became readily available. Although the annual reports of the European Society of Blood and Marrow Transplantation show an important transplant activity in plasma cell disorders in recent years, the real role of the combination of new drugs with graft-versus-myeloma has never been fully explored in this incurable disease. This may partly be attributed to the current limited interest on cell therapy strategies in myeloma. New drugs and graft-versus-myeloma are not mutually exclusive, and their synergy has clearly been shown in relapsed patients."
Those last 2 sentences are points I have made many times here in the Forum.
This is a long paragraph but I have to copy it all to appreciate the last sentence.
"Depth of response is another key factor to predict clinical outcomes in myeloma. Thanks to advanced molecular technology, PCR-based minimal residual disease (MRD) detection currently represents a powerful outcome predictor. In the GIMEMA-VEL-03-096 trial, 39 patients who received consolidation with a combination bortezomib-thalidomide-dexamethasone (VTD) after an autograft were monitored for MRD by qualitative nested-PCR and quantitative PCR (qPCR). After a median follow-up of 8 years, overall survival was 72% for patients in major MRD response versus 48% for those with MRD persistence (P=0.041).17 This was a hallmark study that clearly showed that molecular remissions could be obtained with new drug-based consolidation treatments. However, the same group recently reported on the long-term outcomes of molecular monitoring after a tandem ‘auto-non-myeloablative allo’ approach.18 Twenty-six patients were prospectively evaluated by both nested-PCR and qPCR. Specific markers were generated in 19/26. At the median follow-up of 12.1, overall survival for the whole-patient cohort was not reached and event-free survival was 4 years from the allograft. Rate of nested-PCR negativity increased up to 47% at 1 year after the allograft, whereas the molecular response rate was 63% at 2 years by qPCR. At a remarkable median follow-up of 12.1, median overall survival and event-free survival were not reached in patients who achieved nested-PCR negativity while they were 3.3 and 1.5 years, respectively, in the remaining patients. Graft-versus-myeloma appeared to determine prolonged molecular remission rates, higher than those reported after autografting and VTD. Although the number of patients studied was small, one may provocatively infer that, had these findings been obtained with other treatment modalities, they would have been emphasized more in the scientific community."
I could not agree with that last sentence any more:
"Although the number of patients studied was small, one may provocatively infer that, had these findings been obtained with other treatment modalities, they would have been emphasized more in the scientific community."
Source:
B Bruno, "Allogeneic transplantation for multiple myeloma: yes, no or maybe?," Bone Marrow Transplantation, Feb 22, 2016 (full text of article)
Could you imagine how much press there would be if a new form of immunotherapy could show long term remissions like that?
Mark
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Mark11
Re: Progress toward a multiple myeloma cure?
Thanks for the informative post, Mark.
Those of us that are looking at a potential relapse can only hope that some of the newest drugs like Darzalex (daratumumab) may offer a break through. I have been impressed with some of the initial studies. This CD-38 directed monoclonal antibody is not offering a cure but a new line of attack. It can be combined with a proteasome inhibitor and/or immumomodulatory drugs and dex to give existing patients the potential of long-term remissions after a relapse. Of course quality of life, not to mention the huge medical costs involved, will be a real issue. However, I see this and some of the other newer target drugs now in development, as very positive giving hope that myeloma may be turned into a chronic rather than fatal disease.
Those of us that are looking at a potential relapse can only hope that some of the newest drugs like Darzalex (daratumumab) may offer a break through. I have been impressed with some of the initial studies. This CD-38 directed monoclonal antibody is not offering a cure but a new line of attack. It can be combined with a proteasome inhibitor and/or immumomodulatory drugs and dex to give existing patients the potential of long-term remissions after a relapse. Of course quality of life, not to mention the huge medical costs involved, will be a real issue. However, I see this and some of the other newer target drugs now in development, as very positive giving hope that myeloma may be turned into a chronic rather than fatal disease.
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56