Here's an interesting new study comparing multiple myeloma to blood cancers that are considered curable. This study only looks at patients under 50 years old. Some of the points I drew different conclusions than the authors did, but I thought it was a paper well worth reading.
Reference:
Ravi, P, et al, "Defining cure in multiple myeloma: a comparative study of outcomes of young individuals with myeloma and curable hematologic malignancies," Blood Cancer Journal, Feb 28 2018 (full text of article)
Abstract:
"Advances in therapy in recent years have led investigators to challenge the dogma that multiple myeloma is incurable. We assessed overall (OS) and progression-free survival (PFS) of young patients ( ≤ 50 years) with multiple myeloma and compared outcomes with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and Hodgkin lymphoma (HL). All patients ≤ 50 years with newly diagnosed multiple myeloma (n = 212), FL (n = 168), DLBCL (n = 195), and HL (n = 233) between 1 January 2005 and 31 December 2015 were included. Observed vs. expected survival was summarized by standardized mortality ratios (SMR). Compared to the background US population, excess mortality risk was seen at diagnosis in all four cancers, SMR 19.5 (15.2–24.5) in multiple myeloma, 4.2 (2.3–7.2) in FL, 13.0 (9.2–18.4) in DLBCL, and 5.2 (2.6–9.3) in HL. We reasoned that cure would most likely occur in the first 3 years after diagnosis and be reflected by an overall survival probability similar to the background population. From the 36-month landmark, excess mortality risk was seen in multiple myeloma (SMR 20.7 [14.7–28.3]) and FL (SMR 3.8 [1.5–7.8]), but not with DLBCL (SMR 3.1 [0.8–8.0]) or HL (SMR 0.9 [0.0–5.1]). Multiple myeloma patients have 20-fold excess mortality risk compared to the background population at diagnosis and at 3 years after diagnosis, suggesting that multiple myeloma remains an incurable cancer."
The author's definition of cure:
"Put simply, cure should be viewed as successful delivery of treatment(s) for a defined period of time with subsequent complete resolution of the disease. The patient should then expect to be able to enjoy a quantity and quality of life comparable with healthy counterparts once treatment has been completed. Although occasional patients with almost any disease may meet the definition of having achieved a cure, the point at which a disease as a whole can be considered curable requires that a predictable percentage of patients must achieve this state."
Authors on the history of the definition of cure:
"In 1963, Easson and Russel, writing in the British Medical Journal, provided the first definition of ‘‘cure’’ in cancer, noting that it should “connote that in time – probably a decade or two after treatment – there remains a group of disease-free survivors whose annual death rate from all causes is similar to that of a normal population group of the same sex and age distribution.” This was further extended by Frei and Gehan in 1971 to include that cure should be “unassociated with continuing morbidity from the disease or its treatment”. The time-dependent concept of cure was further refined by Frei, who argued that the particular time point – typically between 1–5 years in most curable cancers – at which the plateau in disease-free survival ought to occur (to signify cure) varies depending on the disease kinetics of a particular tumor."
The authors discussing their thoughts on aggressive therapy in myeloma using standard therapies:
"In 2014, an update of the ‘‘total therapy’’ (TT) trials conducted at the University of Arkansas reported a ‘‘cure fraction’’ of almost 50% among all patients treated under the TT3a protocol. This number, derived from a mathematical model, led them to conclude that multiple myeloma had joined the “club of curable malignancies”. Although one cannot fail to be impressed by the Arkansas outcomes, two points must be appreciated. Firstly, comparison of the OS and PFS curves for multiple myeloma with those for HL and DLBCL highlight that the level of ‘‘cure’’ achieved with multiple myeloma is not that which is seen with the latter two cancers. This is supported by multi-institutional data showing that multiple myeloma patients under the age of 50 lose an average of more than 25 years of life compared to healthy population controls. Second, the treatment of multiple myeloma (in our patients and with TT) incorporates a prolonged period of maintenance therapy in contrast to HL or DLBCL, where therapy is limited to a defined number of cycles, with no evidence for a survival benefit arising from adjuvant or maintenance therapy. Sustained CR in a subset of patients with multiple myeloma enrolled in a very cumbersome clinical trial receiving years of continuous ongoing therapy is, in our opinion, not the same as showing a clear plateau in OS and PFS in patients treated with an intent to cure."
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Re: Defining a cure for multiple myeloma (new study)
Hello Mark11,
That is an interesting paper comparing outcomes with myeloma to those in other blood cancers.
Although we do not seem to be at a 'cure' yet, I found the EMN02/H095 study, whose phase 3 results were presented at ASH 2017, to be interesting too.
https://ash.confex.com/ash/2017/webprogram/Paper102360.html
In a large study of about 1000 participants, there were two randomization trials. One was to compare having an autologous stem cells transplant, and one not . Consolidation was also randomized.
As well as that, single transplants were compared to tandem transplants. Especially for patients with high risk cytogenetics, double transplants seemed to give an advantage.
So it seems that survival rates are gradually increasing, due to combinations of newer and older treatments.
That is an interesting paper comparing outcomes with myeloma to those in other blood cancers.
Although we do not seem to be at a 'cure' yet, I found the EMN02/H095 study, whose phase 3 results were presented at ASH 2017, to be interesting too.
https://ash.confex.com/ash/2017/webprogram/Paper102360.html
In a large study of about 1000 participants, there were two randomization trials. One was to compare having an autologous stem cells transplant, and one not . Consolidation was also randomized.
As well as that, single transplants were compared to tandem transplants. Especially for patients with high risk cytogenetics, double transplants seemed to give an advantage.
So it seems that survival rates are gradually increasing, due to combinations of newer and older treatments.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Defining a cure for multiple myeloma (new study)
If you look at the table with treatment regimens, it is obvious that no people get more advanced treatment.
Re: Defining a cure for multiple myeloma (new study)
Hello,
In this study, I think that CyBorD (cyclophosphamide, Velcade, and dexamethasone) is considered to be an advanced treatment. Velcade is a relatively recent treatment, of about 10-15 years or less. Of course, now there are more recent developments, such as the monoclonal antibodies, CAR T-cell treatments, and other drugs that target other pathways, but the authors' premise is that an autologous stem cell transplant is still helpful.
In this study, I think that CyBorD (cyclophosphamide, Velcade, and dexamethasone) is considered to be an advanced treatment. Velcade is a relatively recent treatment, of about 10-15 years or less. Of course, now there are more recent developments, such as the monoclonal antibodies, CAR T-cell treatments, and other drugs that target other pathways, but the authors' premise is that an autologous stem cell transplant is still helpful.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Defining a cure for multiple myeloma (new study)
Nancy S.,
I think you may be misunderstanding the point of the article. The article is about curing younger patients, not increasing overall survival. As an example, standard risk DLBCL patients typically do 6 cycles of R-CHOP. They do no maintenance and do no transplants as part of their upfront therapy. As the article shows, if they are in remission at 3 years, it is highly likely they will not relapse and have a lifespan on par with the general population. Doing more transplants, using more / newer drugs for longer periods of time, etc, reinforces the authors' point that myeloma is not a curable cancer using standard therapies.
Zakhar,
You wrote:
I am not sure what table or what treatment you are referring to, but do you think there is an approved therapy combination available to myeloma patients currently that can be delivered as part of their upfront therapy in a fixed number of cycles, that would cure a reasonably high percentage of myeloma patients? If so, what one?
Mark
I think you may be misunderstanding the point of the article. The article is about curing younger patients, not increasing overall survival. As an example, standard risk DLBCL patients typically do 6 cycles of R-CHOP. They do no maintenance and do no transplants as part of their upfront therapy. As the article shows, if they are in remission at 3 years, it is highly likely they will not relapse and have a lifespan on par with the general population. Doing more transplants, using more / newer drugs for longer periods of time, etc, reinforces the authors' point that myeloma is not a curable cancer using standard therapies.
Zakhar,
You wrote:
"If you look at the table with treatment regimens, it is obvious that no people get more advanced treatment."
I am not sure what table or what treatment you are referring to, but do you think there is an approved therapy combination available to myeloma patients currently that can be delivered as part of their upfront therapy in a fixed number of cycles, that would cure a reasonably high percentage of myeloma patients? If so, what one?
Mark
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Mark11
Re: Defining a cure for multiple myeloma (new study)
Hi Mark,
No, I don't know of a positive treatment that would have a remission long enough to be called a cure, although there are long remissions reported from some patients. Some patients have a remission from a stem cell transplant for over three years, for example. I have been one of the luckier patients, having had two drug-free remission's now, but am still aware that another relapse is probably in the cards.
The CAR T-cell approach has been promising too, although it is such a new therapy that there wouldn't be long term results yet either.
Even us 'older' patients hope for a cure, having been diagnosed in my late fifties, that would probably have taken some years off of a projected life span of more than 80 years, statistically!
No, I don't know of a positive treatment that would have a remission long enough to be called a cure, although there are long remissions reported from some patients. Some patients have a remission from a stem cell transplant for over three years, for example. I have been one of the luckier patients, having had two drug-free remission's now, but am still aware that another relapse is probably in the cards.
The CAR T-cell approach has been promising too, although it is such a new therapy that there wouldn't be long term results yet either.
Even us 'older' patients hope for a cure, having been diagnosed in my late fifties, that would probably have taken some years off of a projected life span of more than 80 years, statistically!
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Defining a cure for multiple myeloma (new study)
Mark,
If you look at the "Defining cure in multiple myeloma" article, Table 1, it says that only 15% got an IMID+PI combo, and in the text it is stated that only 52% got a transplant (and these are patients under 50). If current approaches are applied, results would be more optimistic for multiple myeloma patients.
If you look at the "Defining cure in multiple myeloma" article, Table 1, it says that only 15% got an IMID+PI combo, and in the text it is stated that only 52% got a transplant (and these are patients under 50). If current approaches are applied, results would be more optimistic for multiple myeloma patients.
Re: Defining a cure for multiple myeloma (new study)
Hi Nancy and Zakhar,
The reason I posted this study is that many myeloma patients do not seem to understand the difference between a cured patient, a curable disease, a functional cure, etc In my opinion, the authors did an excellent job describing this. It is common for oncology patients to be cured, so I think it is good for myeloma patients to understand what it means when a leukemia patient says they are cured.
With respect to good outcomes, there may be individual myeloma patients that are cured, or have excellent outcomes. However, as the authors state:
"Although occasional patients with almost any disease may meet the definition of having achieved a cure, the point at which a disease as a whole can be considered curable requires that a predictable percentage of patients must achieve this state."
Hi Zakhar
I am a long time poster here on the Beacon, and I did not post about this article to come off as negative. I believe most posters here believe myeloma is not a curable cancer and most patients here are on some form of therapy to help them stay in remission. That is just reality.
With respect to the combination of a proteasome inhibitor (PI), immunodulatory agent (Imid), and dexamethasone and a single upfront auto transplant to single drug IMID maintenance, this study clearly shows that therapy path is not curative for a majority of patients.
Attal, M, et al, "Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma," New England Journal of Medicine, April 6, 2017 (full text of article)
In this study, half the patients in the Revlimid, Velcade, and dexamethasone + auto stem cell transplant + 1-year Imid maintenance group relapsed in 50 months with no plateau in sight.
This purpose of the study I posted about was to define cure and see if myeloma should be considered a curable cancer, not to be "optimistic".
Also note that just because a disease is not curable does not mean it is a poor outcome blood cancer. The authors of the paper I posted about mention chronic myeloid leukemia (CML). I believe the overall survival for younger CML patients is close to 90% at 10 years, yet it could be argued none of them are cured.
Mark
The reason I posted this study is that many myeloma patients do not seem to understand the difference between a cured patient, a curable disease, a functional cure, etc In my opinion, the authors did an excellent job describing this. It is common for oncology patients to be cured, so I think it is good for myeloma patients to understand what it means when a leukemia patient says they are cured.
With respect to good outcomes, there may be individual myeloma patients that are cured, or have excellent outcomes. However, as the authors state:
"Although occasional patients with almost any disease may meet the definition of having achieved a cure, the point at which a disease as a whole can be considered curable requires that a predictable percentage of patients must achieve this state."
Hi Zakhar
I am a long time poster here on the Beacon, and I did not post about this article to come off as negative. I believe most posters here believe myeloma is not a curable cancer and most patients here are on some form of therapy to help them stay in remission. That is just reality.
With respect to the combination of a proteasome inhibitor (PI), immunodulatory agent (Imid), and dexamethasone and a single upfront auto transplant to single drug IMID maintenance, this study clearly shows that therapy path is not curative for a majority of patients.
Attal, M, et al, "Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma," New England Journal of Medicine, April 6, 2017 (full text of article)
In this study, half the patients in the Revlimid, Velcade, and dexamethasone + auto stem cell transplant + 1-year Imid maintenance group relapsed in 50 months with no plateau in sight.
This purpose of the study I posted about was to define cure and see if myeloma should be considered a curable cancer, not to be "optimistic".
Also note that just because a disease is not curable does not mean it is a poor outcome blood cancer. The authors of the paper I posted about mention chronic myeloid leukemia (CML). I believe the overall survival for younger CML patients is close to 90% at 10 years, yet it could be argued none of them are cured.
Mark
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Mark11
Re: Defining a cure for multiple myeloma (new study)
I happened to read that article back around the time Mark posted it and I thought it was quite good. I'm not sure it was all that necessary at this point in time as I don't think there are too many people out there who actually believe that myeloma qualifies as curable. Still, it's good to have a definition of what that actually means as myeloma treatments improve and survival times increase. I do think that we MAY be getting into territory in which myeloma is becoming a chronic disease that is manageable for some people over a long period of time, but that's a very different thing from a cure.
What I find to be very optimistic is that we're even having this sort of discussion. Fifteen years ago, I don't think anyone would have needed reminding that myeloma is not a curable disease.
What I find to be very optimistic is that we're even having this sort of discussion. Fifteen years ago, I don't think anyone would have needed reminding that myeloma is not a curable disease.
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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: Defining a cure for multiple myeloma (new study)
Yes, thanks for posting this Mark, and I agree with your comments too Mike F. When I was a newly diagnosed patient, I read statistics concerning five year survival rates, which were not over 50 percent, as I recall. I think that those rates are steadily climbing and have not 'plateaued' yet. Interesting that even now in this study, a differentiation is made between progression free survival (PFS) and overall survival (OS). The PFS seemed to increase but not the OS. And the study criteria did preclude many patients due to health concerns, so in reality the results of the study would probably be not as positive if all patients were included.
But that is what myeloma research is all about, to steadily push back the disease. Note also that newer treatments, such as monoclonal antibody treatments, are not included in this study. When the results are in from phase 3 trials of all of the really new drugs, we may see a big leap in PFS and OS.
But that is what myeloma research is all about, to steadily push back the disease. Note also that newer treatments, such as monoclonal antibody treatments, are not included in this study. When the results are in from phase 3 trials of all of the really new drugs, we may see a big leap in PFS and OS.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
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