With all these latest new drugs, vaccines, t-cells whatever you call them, does anyone believe there will be a cure in the next ten years?
I am hoping that newly diagnosed on VRD, perhaps stem cell transplant, maintenance drugs will keep my mom alive for another 10 years seeing she is a normal risk candidate. Am I giving myself false hope? My heart is breaking for my mom : / (and for all others with this HELL)
Forums
Re: Will there be a myeloma cure in the next 10 years?
At this stage the more realistic goal is to make myeloma a chronic disease like diabetes. Diabetes is not curable but nonetheless people live long and relatively comfortable lives with the disease (to name one, my father).
The main obstacle in accomplishing this is the tendency of most myeloma patients to relapse. Considering that the causes for relapse are poorly understood (just in the last few years there has been some breakthrough in that regard), it is safe to say that making myeloma a chronic disease may be some ways down the road.
Cure is a whole separate issue. This is not to say that some patients don't live long and comfortable lives. I know that all of us here hope for such lives. Regrettably, at least from my layman understanding of the state of myeloma research, the best I personally hope for is a working cocktail of drugs until the rest of my life. I just turned 40 (surviving for 3 years so far).
Good luck to your mom and I apologize if this is not what you expected to hear. Just one man's opinion. Hope is wonderful, but it often does not go hand in hand with statistics. Again, best of luck.
The main obstacle in accomplishing this is the tendency of most myeloma patients to relapse. Considering that the causes for relapse are poorly understood (just in the last few years there has been some breakthrough in that regard), it is safe to say that making myeloma a chronic disease may be some ways down the road.
Cure is a whole separate issue. This is not to say that some patients don't live long and comfortable lives. I know that all of us here hope for such lives. Regrettably, at least from my layman understanding of the state of myeloma research, the best I personally hope for is a working cocktail of drugs until the rest of my life. I just turned 40 (surviving for 3 years so far).
Good luck to your mom and I apologize if this is not what you expected to hear. Just one man's opinion. Hope is wonderful, but it often does not go hand in hand with statistics. Again, best of luck.
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ivanm - Name: Ivan Mitev
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August, 2011
- Age at diagnosis: 37
Re: Will there be a myeloma cure in the next 10 years?
Hi Hopeful27,
I actually think there is an accepted cure for younger multiple myeloma patients - allo transplant done in first complete response (optimally), or allo done to consolidate initial response. Typically blood cancer patients can only be cured by the therapy they do after being diagnosed. There are some examples of blood cancer patients that are cured by allo transplant after relapse, but the percentage is low. It would be a big step forward to find a therapy that could cure myeloma patients after they have relapsed.
The second point I would make is that the myeloma stem cell / progenitor cell(s) has not been positively identified. In order to cure patients with "targeted" therapies, the doctors would need to know what they are targeting. When you look at the example of allo transplant as a potentially curative therapy, they are often a high dose of a non-specific drug like an alkylator followed up with a comprehensive form of immunotherapy (new immune system). That is a lot different that immunotherapies that have only one target (ex. CAR T cells targeting CD19 for acute lymphoblastic leukemia).
Just know that something that puts a myeloma patient into remission (ex. Velcade, Kyprolis, Pomalyst, Revlimid, etc) may have no effect on the stem / progenitor cell(s). The opposite is true as well. Allo transplant can be very effective at keeping a patient in CR if the therapy is done with a patient already in a chemotherapy-induced first CR, but allos tend to not be very effective when done on relapsed patients/those with advancing disease.
I mention that because it is difficult to get a therapy approved that "just" keeps a patient in remission, since therapies are initially judged in clinical trials by their ability to get a response against active disease. Having said that, Gleevec can get a patient to remission and hold it long term for some patients with CML (chronic myelogenous leukemia), but I do not think there is any myeloma therapy that is considered as effective as Gleevec is for CML patients.
IMO it is more realistic to hope for myeloma becoming a chronic disease for most standard risk patients with newer treatments that have less side effects than drugs like Revlimid, Kyprolis, Velcade, etc in the next decade. Most newly diagnosed patients are approximately 70 years old with standard risk disease, so a true cure, while nice to talk about, is probably not as important as newer therapies with less side effects than the current ones that can keep most patients in remission for long periods with a good quality of life.
Truly curative therapy is really only important for a small percentage of younger myeloma patients like me. My experience with allo transplant has been very positive, so I am satisfied with the therapies that were available to me as a younger patient at the time of diagnosis (2010).
Mark
I actually think there is an accepted cure for younger multiple myeloma patients - allo transplant done in first complete response (optimally), or allo done to consolidate initial response. Typically blood cancer patients can only be cured by the therapy they do after being diagnosed. There are some examples of blood cancer patients that are cured by allo transplant after relapse, but the percentage is low. It would be a big step forward to find a therapy that could cure myeloma patients after they have relapsed.
The second point I would make is that the myeloma stem cell / progenitor cell(s) has not been positively identified. In order to cure patients with "targeted" therapies, the doctors would need to know what they are targeting. When you look at the example of allo transplant as a potentially curative therapy, they are often a high dose of a non-specific drug like an alkylator followed up with a comprehensive form of immunotherapy (new immune system). That is a lot different that immunotherapies that have only one target (ex. CAR T cells targeting CD19 for acute lymphoblastic leukemia).
Just know that something that puts a myeloma patient into remission (ex. Velcade, Kyprolis, Pomalyst, Revlimid, etc) may have no effect on the stem / progenitor cell(s). The opposite is true as well. Allo transplant can be very effective at keeping a patient in CR if the therapy is done with a patient already in a chemotherapy-induced first CR, but allos tend to not be very effective when done on relapsed patients/those with advancing disease.
I mention that because it is difficult to get a therapy approved that "just" keeps a patient in remission, since therapies are initially judged in clinical trials by their ability to get a response against active disease. Having said that, Gleevec can get a patient to remission and hold it long term for some patients with CML (chronic myelogenous leukemia), but I do not think there is any myeloma therapy that is considered as effective as Gleevec is for CML patients.
IMO it is more realistic to hope for myeloma becoming a chronic disease for most standard risk patients with newer treatments that have less side effects than drugs like Revlimid, Kyprolis, Velcade, etc in the next decade. Most newly diagnosed patients are approximately 70 years old with standard risk disease, so a true cure, while nice to talk about, is probably not as important as newer therapies with less side effects than the current ones that can keep most patients in remission for long periods with a good quality of life.
Truly curative therapy is really only important for a small percentage of younger myeloma patients like me. My experience with allo transplant has been very positive, so I am satisfied with the therapies that were available to me as a younger patient at the time of diagnosis (2010).
Mark
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Mark
Re: Will there be a myeloma cure in the next 10 years?
Hi Mark, one question. I'm from the same group as you (39 years old). My doc said, a double auto would be as good as an allo, because of the high risk of HOGD. Did you have a donor from your family or an external mach for the allo? How did you rated your risk in 2010 when you did that allo. THX, Thomas
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Thomas
Re: Will there be a myeloma cure in the next 10 years?
I'm not confident that there will be a cure in 10 years or less, but there is a lot of progress in available treatments. I lost my sister to the disease in '95 and she had few options and didn't last long after diagnoses. I'm 5 years away from my diagnoses and while I'm back on a treatment, the treatment is being started very early in my relapse.
As far as keeping your mom alive for another 10 years? No reason to think it isn't possible.
As far as keeping your mom alive for another 10 years? No reason to think it isn't possible.
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Wayne K - Name: Wayne
- Who do you know with myeloma?: Myself, my sister who passed in '95
- When were you/they diagnosed?: 03/09
- Age at diagnosis: 70
Re: Will there be a myeloma cure in the next 10 years?
Hi Thomas,
I am guessing you meant GVHD. My patient level read of the risk of GVHD is that it depends on how the transplant is done as opposed to who your donor is in 2014. Here is a study of relapsed patients that did fully t cell depleted allos that show none of the patients having a problem with chronic GVHD.
"34 pts with a median follow up of 31.6mos (range: 7.6 – 65.1 mos) of survivors are reported, median age 56 years (range 32 – 69). All pts engrafted promptly (median d+10, range d+9 to +12).TRM and acute GvHD (grade II-IV) at 12mos is 9% (95% CI: 2% – 23%) and 6% (95% CI: 1% – 17%). Chronic GvHD was not observed in any pt."
https://myelomabeacon.org/resources/mtgs/ash2013/abs/2115/
On the other hand, a mini allo with no graft manipulation/no use of ATG could result in chronic GVHD rates of up to 85%.
"After a median follow-up of 7 years, cumulative incidences of grade II-IV acute and extensive chronic GVHD were 9% (95%CI: 4-15) and 85% (75-91) respectively. "
https://myelomabeacon.org/resources/mtgs/ash2013/abs/3353/
I had an unrelated female donor and I did what is considered a partially t cell depleted allo. I used ATG to control chronic GVHD. I had what would be called limited chronic gvhd for one month after I discontinued my immunosuppressive drugs 6 months after transplant. Of the matched pairs, female donor to male is considered having a high risk for extensive chronic GVHD with an un-manipulated graft.
I currently have no signs of GVHD and, other than the damage done to my spine by the cancer, my quality of life is back to what it was prior to diagnosis. I actually consider limited chronic GVHD a great thing since having it is associated with less chance of relapse.
"In conclusion, patients with multiple myeloma can have an excellent overall survival following allogeneic transplantation even in the setting of relapsed or refractory disease to a prior auto HSCT. Unrelated donors performed just as well as matched siblings. Acute GVHD was deleterious to OS, whereas chronic GVHD was significantly associated with improvement in OS supporting the role of a graft versus tumor effect in multiple myeloma."
https://myelomabeacon.org/resources/mtgs/ash2013/abs/2154/
My view on tandem autos is that they do not address the real problem I view a myeloma patient as having. Our immune system makes plasma cells - myeloma is a cancer of the plasma cells. Our immune system does not identify the cancer as foreign and kill it - a donor immune system can. Twice as much melphalan does not correct the problem, in my opinion. As I mentioned above, you and I are not the typical myeloma patient. A tandem auto could very well be "just as good" as an allo for the typical myeloma patient, but I doubt it would have been for me.
I am a high risk patient. Using drugs (standard or high dose) the doctors I consulted with thought I would get to CR but it would only last about 12-20 months. Most patients are not as a high risk as I am. I would say doing the allo makes it much more likely that I would be a long term survivor (10 years plus). In my opinion, it would have been much more "risky" for me to not do the allo and rely on drugs to make me a long term survivor.
Mark
I am guessing you meant GVHD. My patient level read of the risk of GVHD is that it depends on how the transplant is done as opposed to who your donor is in 2014. Here is a study of relapsed patients that did fully t cell depleted allos that show none of the patients having a problem with chronic GVHD.
"34 pts with a median follow up of 31.6mos (range: 7.6 – 65.1 mos) of survivors are reported, median age 56 years (range 32 – 69). All pts engrafted promptly (median d+10, range d+9 to +12).TRM and acute GvHD (grade II-IV) at 12mos is 9% (95% CI: 2% – 23%) and 6% (95% CI: 1% – 17%). Chronic GvHD was not observed in any pt."
https://myelomabeacon.org/resources/mtgs/ash2013/abs/2115/
On the other hand, a mini allo with no graft manipulation/no use of ATG could result in chronic GVHD rates of up to 85%.
"After a median follow-up of 7 years, cumulative incidences of grade II-IV acute and extensive chronic GVHD were 9% (95%CI: 4-15) and 85% (75-91) respectively. "
https://myelomabeacon.org/resources/mtgs/ash2013/abs/3353/
I had an unrelated female donor and I did what is considered a partially t cell depleted allo. I used ATG to control chronic GVHD. I had what would be called limited chronic gvhd for one month after I discontinued my immunosuppressive drugs 6 months after transplant. Of the matched pairs, female donor to male is considered having a high risk for extensive chronic GVHD with an un-manipulated graft.
I currently have no signs of GVHD and, other than the damage done to my spine by the cancer, my quality of life is back to what it was prior to diagnosis. I actually consider limited chronic GVHD a great thing since having it is associated with less chance of relapse.
"In conclusion, patients with multiple myeloma can have an excellent overall survival following allogeneic transplantation even in the setting of relapsed or refractory disease to a prior auto HSCT. Unrelated donors performed just as well as matched siblings. Acute GVHD was deleterious to OS, whereas chronic GVHD was significantly associated with improvement in OS supporting the role of a graft versus tumor effect in multiple myeloma."
https://myelomabeacon.org/resources/mtgs/ash2013/abs/2154/
My view on tandem autos is that they do not address the real problem I view a myeloma patient as having. Our immune system makes plasma cells - myeloma is a cancer of the plasma cells. Our immune system does not identify the cancer as foreign and kill it - a donor immune system can. Twice as much melphalan does not correct the problem, in my opinion. As I mentioned above, you and I are not the typical myeloma patient. A tandem auto could very well be "just as good" as an allo for the typical myeloma patient, but I doubt it would have been for me.
I am a high risk patient. Using drugs (standard or high dose) the doctors I consulted with thought I would get to CR but it would only last about 12-20 months. Most patients are not as a high risk as I am. I would say doing the allo makes it much more likely that I would be a long term survivor (10 years plus). In my opinion, it would have been much more "risky" for me to not do the allo and rely on drugs to make me a long term survivor.
Mark
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Mark
Re: Will there be a myeloma cure in the next 10 years?
Mark,
Thanks for replying. Sorry, I am new to all this, so I am trying to figure out terms, etc. If you don't mind me asking, are you still in complete remission? My mom is "standard risk". If it were you, would you still have accepted a donor over your own?
Thanks so much for any advice.
J.
Thanks for replying. Sorry, I am new to all this, so I am trying to figure out terms, etc. If you don't mind me asking, are you still in complete remission? My mom is "standard risk". If it were you, would you still have accepted a donor over your own?
Thanks so much for any advice.
J.
Re: Will there be a myeloma cure in the next 10 years?
Regarding the allo and Mark's experience with it, I'd say that Mark is quite a fortunate individual. There is no dispute whatsoever that allo could be curative. However, many have died in that pursuit and many have relapsed. To me a cure is something that is proven to work almost universally, or at least, for majority of the patients. To the best of my knowledge, allo (T cell deplete or not, DLI induced or not, reduced intensity or standard conditioning) has not achieved such status and probably never will.
To quote Giralt and Koehne from “Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: What Place, If Any?” (something everyone considering an allo should read): "Despite the curative potential of allogeneic hematopoietic stem cell transplantation (allo HSCT) for patients with multiple myeloma (multiple myeloma) and reduction of transplant-related mortality with non-myeloablative transplant approaches, the role of this treatment modality in the care of multiple myeloma patients remains controversial."
This comes from two of the most recognized transplant doctors in the country. Depending on the regimen, the various allo studies show a 2 year overall survival from 31% to 78%. When you add lenalidomide [Revlimid], things can look a bit better with a 3 year OS of 85%.
The catch with the transplant, however, is that by reducing the chance of morbidity you are also reducing the chance of a cure. That's why people like Koehne and Giralt are working diligently to bridge this gap by using novel strategies such as WT1 tumor engineering. Whether that would pan out or not, or when, I do not know. I am happy however, that I have that venue as an option.
Aside from the issue of whether they will be able to bridge the morbidity and relapse problem, the current state of affairs is depicted by the 2013 study from City of Hope which I think is by far with one of the longest follow ups (median of 9.8 yrs) and shows a surprising rate of late relapses (10% relapsing b/n 6 and 12 years). To quote from the study, "Among the six late relapse patients, all were transplanted within 14 months of diagnosis, five had normal karyotypes, and five were in CR/PR. Our data provide additional evidence that, while survival may be extended by reduced intensity allogeneic transplant, ultimately, it may not offer a cure."
To quote further "Furthermore, we saw no plateau in the relapse incidence curve and late relapses continued to occur, even as late as 11.5 years post-transplant." Lastly, "[t]he phenomenon of late relapses in this study may suggest the presence of heterogeneous malignant clones that survived RIC and arose after a long period of dormancy." (http://www.ncbi.nlm.nih.gov/pubmed/23151215)
In other words, I second what Mark says and I am a firm believer -- for myself at least -- that, if anything will cure me, it will be an allo transplant (despite the fact that I missed the boat on doing it at first response – I was too chicken). Still, I don't think that this really falls within the colloquial understanding of a cure. Being cured by an allo is rather an outlier beating the odds. That's how I understand it at least.
Good luck.
To quote Giralt and Koehne from “Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: What Place, If Any?” (something everyone considering an allo should read): "Despite the curative potential of allogeneic hematopoietic stem cell transplantation (allo HSCT) for patients with multiple myeloma (multiple myeloma) and reduction of transplant-related mortality with non-myeloablative transplant approaches, the role of this treatment modality in the care of multiple myeloma patients remains controversial."
This comes from two of the most recognized transplant doctors in the country. Depending on the regimen, the various allo studies show a 2 year overall survival from 31% to 78%. When you add lenalidomide [Revlimid], things can look a bit better with a 3 year OS of 85%.
The catch with the transplant, however, is that by reducing the chance of morbidity you are also reducing the chance of a cure. That's why people like Koehne and Giralt are working diligently to bridge this gap by using novel strategies such as WT1 tumor engineering. Whether that would pan out or not, or when, I do not know. I am happy however, that I have that venue as an option.
Aside from the issue of whether they will be able to bridge the morbidity and relapse problem, the current state of affairs is depicted by the 2013 study from City of Hope which I think is by far with one of the longest follow ups (median of 9.8 yrs) and shows a surprising rate of late relapses (10% relapsing b/n 6 and 12 years). To quote from the study, "Among the six late relapse patients, all were transplanted within 14 months of diagnosis, five had normal karyotypes, and five were in CR/PR. Our data provide additional evidence that, while survival may be extended by reduced intensity allogeneic transplant, ultimately, it may not offer a cure."
To quote further "Furthermore, we saw no plateau in the relapse incidence curve and late relapses continued to occur, even as late as 11.5 years post-transplant." Lastly, "[t]he phenomenon of late relapses in this study may suggest the presence of heterogeneous malignant clones that survived RIC and arose after a long period of dormancy." (http://www.ncbi.nlm.nih.gov/pubmed/23151215)
In other words, I second what Mark says and I am a firm believer -- for myself at least -- that, if anything will cure me, it will be an allo transplant (despite the fact that I missed the boat on doing it at first response – I was too chicken). Still, I don't think that this really falls within the colloquial understanding of a cure. Being cured by an allo is rather an outlier beating the odds. That's how I understand it at least.
Good luck.
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ivanm - Name: Ivan Mitev
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August, 2011
- Age at diagnosis: 37
Re: Will there be a myeloma cure in the next 10 years?
Hi Hopeful27,
I just found out this week that I am still in CR. I have only been in CR for 3 years.
I would have still done an upfront allo even if I was standard risk. My reasoning is based on a few factors. The first is long term quality of life. Studies of long term survivors of allo transplant show that long term QOL of allo transplant survivors is typically on par with the general population if the patient does not have extensive chronic GVHD.
"The aims of the study were to: (1) explore the baseline and change over time in these health outcomes, and (2) characterize subgroups experiencing adverse outcomes. In this longitudinal study, adults who survived >3 years from date of allogeneic HSCT completed a series of patient-reported outcome measures annually, including measures of health status, HRQL, and symptoms. Data were analyzed using hierarchical linear modeling. Subjects (N = 171) were on average 44 (±13.5) years of age and primarily male (62.6%); 40% were Hispanic. Mean scores for physical and mental health and HRQL were preserved relative to population norms. Hierarchical linear modeling revealed no significant change in the mean trajectories of these outcomes, although significant between-individual variability was observed. When controlling for demographic and clinical factors, physical symptom distress negatively affected all outcomes. The impact of symptom distress on physical health varied based on time since HSCT; impairment in physical health was greatest in survivors experiencing high symptom distress and who were within the first decade post transplantation. Extended treatment with systemic immunosuppressive therapy also predicted inferior physical health. These findings suggest that patient-centered outcomes are preserved relative to normative values and are generally stable after allogeneic HSCT, although survivors with persistent symptoms and those receiving systemic immunosuppression experience impairments in health status and HRQL."
http://www.ncbi.nlm.nih.gov/pubmed/24355521
Systematic immunosuppressive therapy is required for patients with extensive chronic GVHD.
"The main outcomes examined were chronic graft-versus-host-disease, disease relapse, survival, health-related quality-of-life (HRQL) (Functional Assessment of Cancer Therapy-General), physical and mental health (SF-36), and symptom experience (Rotterdam Symptom Checklist). Seventy-five (82%) of 92 survivors no longer required systemic immunosuppressive treatment. Four (4.3%) relapsed with leukemia at a median of 8.5 years (range: 6.2-14.0) after HSCT. Four (4.3%) died between 7.4 and 13.4 years post-HSCT (1 relapse, 1 lung cancer, 1 pneumonia, 1 brain hemorrhage). Most survivors beyond 5 years had an excellent performance status with no difference in physical and mental health and higher HRQL scores (P = .02) compared with population norms. Although physical and psychologic symptom distress was low, those with higher symptom distress experienced inferior HRQL. These results show that 5 or more years after T cell-depleted HSCT for hematologic malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent HRQL."
http://www.ncbi.nlm.nih.gov/pubmed/20302959
The example I would point to is Robin Roberts. She did a t cell depleted allo and seems to be back to normal. I happened to be home this AM and it looks like she is doing great.
I would not do an allo in a relapsed setting. In my opinion, the risk does not justify the reward in a relapsed setting. This study shows the difference between doing an allo as part of upfront therapy as opposed to in a relapsed setting. These patients did not have novel agents to get them into remission. Doing the allo in first complete response gave me the piece of mind of knowing I was not going to have battle advancing disease immediately after the transplant. That must be a tough spot to be in. Since myeloma patients have few treatment options not doing an allo as part of upfront therapy would have taken an option away from me. Other patients are willing to do allos in a relapsed setting.
https://ash.confex.com/ash/2011/webprogram/Paper37067.html
I would be uncomfortable taking drugs like IMIDs [Revlimid, Pomalyst/Imnovid, thalidomide] and proteasome inhibitors [Velcade, Kyprolis] long term because the long term health impacts are unknown. Most patients are comfortable with that as opposed to an allo transplant, so I know I am in a very small minority there. I am much more comfortable with therapies that have a long term track record of keeping patients in remission and the long term health related QOL of the survivors is known.
It was actually an easy decision for me to do the allo. My doctor and I barely discussed doing an upfront auto because I wanted the best chance of not relapsing and getting my "old life" back. Only one therapy offered me that opportunity.
Having said that, I did an auto as part of my upfront therapy due to my insurance company and it has had no negative impact on my long term QOL and it upgraded me from VGPR to CR so I was able to do my allo immediately after my auto.
Having said all of that, few myeloma doctors would recommend an allo to a standard risk patient. Fortunately for me, I was originally diagnosed by one that does offer them to all of her younger patients who she feels are healthy enough to do an allo. She is a big believer in immunotherapy.
Mark
I just found out this week that I am still in CR. I have only been in CR for 3 years.
I would have still done an upfront allo even if I was standard risk. My reasoning is based on a few factors. The first is long term quality of life. Studies of long term survivors of allo transplant show that long term QOL of allo transplant survivors is typically on par with the general population if the patient does not have extensive chronic GVHD.
"The aims of the study were to: (1) explore the baseline and change over time in these health outcomes, and (2) characterize subgroups experiencing adverse outcomes. In this longitudinal study, adults who survived >3 years from date of allogeneic HSCT completed a series of patient-reported outcome measures annually, including measures of health status, HRQL, and symptoms. Data were analyzed using hierarchical linear modeling. Subjects (N = 171) were on average 44 (±13.5) years of age and primarily male (62.6%); 40% were Hispanic. Mean scores for physical and mental health and HRQL were preserved relative to population norms. Hierarchical linear modeling revealed no significant change in the mean trajectories of these outcomes, although significant between-individual variability was observed. When controlling for demographic and clinical factors, physical symptom distress negatively affected all outcomes. The impact of symptom distress on physical health varied based on time since HSCT; impairment in physical health was greatest in survivors experiencing high symptom distress and who were within the first decade post transplantation. Extended treatment with systemic immunosuppressive therapy also predicted inferior physical health. These findings suggest that patient-centered outcomes are preserved relative to normative values and are generally stable after allogeneic HSCT, although survivors with persistent symptoms and those receiving systemic immunosuppression experience impairments in health status and HRQL."
http://www.ncbi.nlm.nih.gov/pubmed/24355521
Systematic immunosuppressive therapy is required for patients with extensive chronic GVHD.
"The main outcomes examined were chronic graft-versus-host-disease, disease relapse, survival, health-related quality-of-life (HRQL) (Functional Assessment of Cancer Therapy-General), physical and mental health (SF-36), and symptom experience (Rotterdam Symptom Checklist). Seventy-five (82%) of 92 survivors no longer required systemic immunosuppressive treatment. Four (4.3%) relapsed with leukemia at a median of 8.5 years (range: 6.2-14.0) after HSCT. Four (4.3%) died between 7.4 and 13.4 years post-HSCT (1 relapse, 1 lung cancer, 1 pneumonia, 1 brain hemorrhage). Most survivors beyond 5 years had an excellent performance status with no difference in physical and mental health and higher HRQL scores (P = .02) compared with population norms. Although physical and psychologic symptom distress was low, those with higher symptom distress experienced inferior HRQL. These results show that 5 or more years after T cell-depleted HSCT for hematologic malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent HRQL."
http://www.ncbi.nlm.nih.gov/pubmed/20302959
The example I would point to is Robin Roberts. She did a t cell depleted allo and seems to be back to normal. I happened to be home this AM and it looks like she is doing great.
I would not do an allo in a relapsed setting. In my opinion, the risk does not justify the reward in a relapsed setting. This study shows the difference between doing an allo as part of upfront therapy as opposed to in a relapsed setting. These patients did not have novel agents to get them into remission. Doing the allo in first complete response gave me the piece of mind of knowing I was not going to have battle advancing disease immediately after the transplant. That must be a tough spot to be in. Since myeloma patients have few treatment options not doing an allo as part of upfront therapy would have taken an option away from me. Other patients are willing to do allos in a relapsed setting.
https://ash.confex.com/ash/2011/webprogram/Paper37067.html
I would be uncomfortable taking drugs like IMIDs [Revlimid, Pomalyst/Imnovid, thalidomide] and proteasome inhibitors [Velcade, Kyprolis] long term because the long term health impacts are unknown. Most patients are comfortable with that as opposed to an allo transplant, so I know I am in a very small minority there. I am much more comfortable with therapies that have a long term track record of keeping patients in remission and the long term health related QOL of the survivors is known.
It was actually an easy decision for me to do the allo. My doctor and I barely discussed doing an upfront auto because I wanted the best chance of not relapsing and getting my "old life" back. Only one therapy offered me that opportunity.
Having said that, I did an auto as part of my upfront therapy due to my insurance company and it has had no negative impact on my long term QOL and it upgraded me from VGPR to CR so I was able to do my allo immediately after my auto.
Having said all of that, few myeloma doctors would recommend an allo to a standard risk patient. Fortunately for me, I was originally diagnosed by one that does offer them to all of her younger patients who she feels are healthy enough to do an allo. She is a big believer in immunotherapy.
Mark
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Mark
Re: Will there be a myeloma cure in the next 10 years?
Hi IvanM.
I do not think I wrote anything that would disagree with either of the studies you showed. I have the utmost respect for Dr. Koehne, Giralt and the all of the doctors (especially Dr. Forman) in the second study. I read anything those doctors write about transplantation.
I clearly stated that most myeloma patients do not need allo transplant. It is not a therapy that is typically appropriate for 70 year olds. We are in a small minority of patients that are this young.
"Despite the curative potential of allogeneic hematopoietic stem cell transplantation (allo HSCT) for patients with multiple myeloma (multiple myeloma) and reduction of transplant-related mortality with non-myeloablative transplant approaches, the role of this treatment modality in the care of multiple myeloma patients remains controversial. This controversy is due to the conflicting data emerging from the large cooperative group trials as well as the improvement in outcomes that has been seen with proteosome inhibitors, new immune modulatory drugs as well as the use of post-transplant maintenance therapy. For an individual patient, the risk benefit ratio of allografting remains uncertain. We review the current data and provide recommendations on where and how allo HSCT for myeloma should be further explored."
http://www.ncbi.nlm.nih.gov/pubmed/24146203
For the typical 70 year old standard risk myeloma patient I do not disagree with anything in that abstract.
Every time I mention allo transplant being potentially curative I say it needs to be done in first complete response. Few of the patients in the study you mention appear to be in first complete response. I would not do one in PR. Only one of the late relapses was a patient in CR at the time of transplant.
"For all 6 late-relapse patients the transplant was performed upfront with a median time
from diagnosis of 11 months (range 4.4–14 months). One patient was in CR, 4 in PR and
one was in relapse at the time of transplantation."
Here are the characteristics of all of the patients. That is far from a study of patients that did allos in first CR.
"Patient baseline characteristics are detailed in Table I. The median patient age was 51 years
(32 – 66). Median time from diagnosis to transplant was 9.5 months (0.8–127.0) with 36
patients (60%) receiving early transplant (< 1 year from diagnosis). In the auto-allo group,
30/39 (76.9%) received early transplant (< 1 year from diagnosis) and in the flu-mel group,
6/21 (28.6%) received early transplant. Thirty-eight (63%) patients had chemo-sensitive
disease in complete or partial remission at the time of transplant. Thirty-eight patients had
received induction treatment with chemotherapy only, and 22 patients had received newer
targeted therapies, (thalidomide, lenalidomide, bortezomib) with or without chemotherapy
prior to transplant. All patients (n=39) in the tandem auto-allo group received auto-HCT
prior to allo-HCT in a planned tandem fashion as part of prospective studies investigating
the role of allograft in patients with available human leucocyte antigen (HLA) donors. The
flu-mel patients were selected for allogeneic transplantation based on high-risk features
(progressive or recurrent disease or failed autologous transplant) and were ineligible for a
fully myeloablative allograft based on age or other comorbidities. In the flu-mel group, 4/21
patients had failed prior single-auto-HCT, 5/21 had failed prior tandem-auto-HCT, and 12/21 received RIC allograft as their first transplant. Fifty-nine patients had documented β2-
microglobulin levels at the time of evaluation for transplant. Median β2-microglobulin was
1.9 mg/l (range 0.8–10 mg/l). Fifty-five patients received allogeneic haematopoietic cells
from HLA-matched siblings, and 5 patients, all in the flu-mel group, underwent transplant
from a matched unrelated donor."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542410/pdf/nihms414535.pdf
I do not think there is any study with long term follow up on patients that did allos in first CR for myeloma available since prior to novel agents few patients actually got to CR. I have made it very clear that I do not think allos should be viewed as curative unless the patient is in first CR at the time of transplant. This study seems to be in line with my opinion on this topic.
Mark
I do not think I wrote anything that would disagree with either of the studies you showed. I have the utmost respect for Dr. Koehne, Giralt and the all of the doctors (especially Dr. Forman) in the second study. I read anything those doctors write about transplantation.
I clearly stated that most myeloma patients do not need allo transplant. It is not a therapy that is typically appropriate for 70 year olds. We are in a small minority of patients that are this young.
"Despite the curative potential of allogeneic hematopoietic stem cell transplantation (allo HSCT) for patients with multiple myeloma (multiple myeloma) and reduction of transplant-related mortality with non-myeloablative transplant approaches, the role of this treatment modality in the care of multiple myeloma patients remains controversial. This controversy is due to the conflicting data emerging from the large cooperative group trials as well as the improvement in outcomes that has been seen with proteosome inhibitors, new immune modulatory drugs as well as the use of post-transplant maintenance therapy. For an individual patient, the risk benefit ratio of allografting remains uncertain. We review the current data and provide recommendations on where and how allo HSCT for myeloma should be further explored."
http://www.ncbi.nlm.nih.gov/pubmed/24146203
For the typical 70 year old standard risk myeloma patient I do not disagree with anything in that abstract.
Every time I mention allo transplant being potentially curative I say it needs to be done in first complete response. Few of the patients in the study you mention appear to be in first complete response. I would not do one in PR. Only one of the late relapses was a patient in CR at the time of transplant.
"For all 6 late-relapse patients the transplant was performed upfront with a median time
from diagnosis of 11 months (range 4.4–14 months). One patient was in CR, 4 in PR and
one was in relapse at the time of transplantation."
Here are the characteristics of all of the patients. That is far from a study of patients that did allos in first CR.
"Patient baseline characteristics are detailed in Table I. The median patient age was 51 years
(32 – 66). Median time from diagnosis to transplant was 9.5 months (0.8–127.0) with 36
patients (60%) receiving early transplant (< 1 year from diagnosis). In the auto-allo group,
30/39 (76.9%) received early transplant (< 1 year from diagnosis) and in the flu-mel group,
6/21 (28.6%) received early transplant. Thirty-eight (63%) patients had chemo-sensitive
disease in complete or partial remission at the time of transplant. Thirty-eight patients had
received induction treatment with chemotherapy only, and 22 patients had received newer
targeted therapies, (thalidomide, lenalidomide, bortezomib) with or without chemotherapy
prior to transplant. All patients (n=39) in the tandem auto-allo group received auto-HCT
prior to allo-HCT in a planned tandem fashion as part of prospective studies investigating
the role of allograft in patients with available human leucocyte antigen (HLA) donors. The
flu-mel patients were selected for allogeneic transplantation based on high-risk features
(progressive or recurrent disease or failed autologous transplant) and were ineligible for a
fully myeloablative allograft based on age or other comorbidities. In the flu-mel group, 4/21
patients had failed prior single-auto-HCT, 5/21 had failed prior tandem-auto-HCT, and 12/21 received RIC allograft as their first transplant. Fifty-nine patients had documented β2-
microglobulin levels at the time of evaluation for transplant. Median β2-microglobulin was
1.9 mg/l (range 0.8–10 mg/l). Fifty-five patients received allogeneic haematopoietic cells
from HLA-matched siblings, and 5 patients, all in the flu-mel group, underwent transplant
from a matched unrelated donor."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542410/pdf/nihms414535.pdf
I do not think there is any study with long term follow up on patients that did allos in first CR for myeloma available since prior to novel agents few patients actually got to CR. I have made it very clear that I do not think allos should be viewed as curative unless the patient is in first CR at the time of transplant. This study seems to be in line with my opinion on this topic.
Mark
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Mark
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