Saw an article this morning quoting Dr. Sagar Lonial:
"Five years from now multiple myeloma will have a therapeutic backbone consisting entirely of combinations of novel agents, a leading myeloma researcher predicted.
The combinations will involve immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies. Stem-cell transplantation will retain a role in treatment of myeloma, but its role in the era of monoclonal antibodies will likely be a topic of multiple clinical trials.
“We will sequence patient samples after two to four cycles of therapy in order to understand the specifics of the remaining clone and how to target it,” Sagar Lonial, MD, chief medical officer at Winship Cancer Institute of Emory University said in a presentation at the 2015 Society of Hematologic Oncology annual meeting.
“This will guide maintenance therapy. Once patients become MRD [minimal residual disease] negative, they will be randomized to continue or stop therapy based on their genetics at presentation.”
Perhaps someone could help break this down in layman's terms?
Thanks!
RT
Peace to all, enduring myeloma symptoms and its pharmaceutical interventions ...
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RadiantTiger - Name: Radiant Tiger
- Who do you know with myeloma?: Myself, my deceased uncle
- When were you/they diagnosed?: Feb 2015
- Age at diagnosis: 54
Re: Lonial: Optimistic about cure for multiple myeloma
Hi RT
As I understand it Dr Lonial sees a move in the next five years with research / trials on how to get patients to remission with better use of novel drugs, monoclonal antibodies and stem cell transplants (the latter not being the most prominent treatment necessarily).
He sees short treatment cycles 2-4 cycles followed by I assume bone marrow sampling, to determine which clone(s) remain and gather, I assume, detailed genetic profiling of these remaining clones to target them specifically with some agent. The aim being to get patients to minimal residual disease status and identify suitable maintenance profiles.
The studies will involve patients, once they are of MRD status, being given maintenance or no maintenance based on using their genetic profile on presentation of disease (I assume because they might find people with specific genetic fingerprints who maintain MRD without maintenance and those who do not).
That is how I read this, because there does seem to be an integrated treatment and clinical trials / research perspective to individualise treatments to get optimal responses in his approach to 'cure'.
I am unsure where stem cell transplants would fit in exactly.
Edna.
As I understand it Dr Lonial sees a move in the next five years with research / trials on how to get patients to remission with better use of novel drugs, monoclonal antibodies and stem cell transplants (the latter not being the most prominent treatment necessarily).
He sees short treatment cycles 2-4 cycles followed by I assume bone marrow sampling, to determine which clone(s) remain and gather, I assume, detailed genetic profiling of these remaining clones to target them specifically with some agent. The aim being to get patients to minimal residual disease status and identify suitable maintenance profiles.
The studies will involve patients, once they are of MRD status, being given maintenance or no maintenance based on using their genetic profile on presentation of disease (I assume because they might find people with specific genetic fingerprints who maintain MRD without maintenance and those who do not).
That is how I read this, because there does seem to be an integrated treatment and clinical trials / research perspective to individualise treatments to get optimal responses in his approach to 'cure'.
I am unsure where stem cell transplants would fit in exactly.
Edna.
Re: Lonial: Optimistic about cure for multiple myeloma
Thanks for sharing.
I read it as "we will have the ability to determine the genetic profile of a patient and exactly determine which agents will help get to MRD. Based on the above we will also be able to define if maintenance, no maintenance, or transplant would be necessary".
If they can do this the first time around for any myeloma patient then when/if a new clone expresses itself they will be able to follow the same procedure and keep on treating patients until they achieve MRD.
It's very exciting to read ...
I read it as "we will have the ability to determine the genetic profile of a patient and exactly determine which agents will help get to MRD. Based on the above we will also be able to define if maintenance, no maintenance, or transplant would be necessary".
If they can do this the first time around for any myeloma patient then when/if a new clone expresses itself they will be able to follow the same procedure and keep on treating patients until they achieve MRD.
It's very exciting to read ...
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Cedb
Re: Lonial: Optimistic about cure for multiple myeloma
I wonder ... newer isn't always better.
Alklyators, anthracylcines, etc continue to be used by some specialists in combination with novel agents with very good results. I am by no means a doctor, but I can definitely picture some specialists combining these older, tried-and-true agents with the newer generations of drugs in the coming years – and not exclusively relying on the newer generations of drugs for their treatment plans.
Don't get me wrong, I believe that there will be much better options with less side effects that will make a big difference in treating patients and improving their overall survival (OS) and QOL in the coming years – and I look forward to those improvements in treatments. But will the treatments really be based exclusively on the newer agents?
There are also many patients in many countries who are having a heck of time just getting access to the current generations of drugs available in the USA. Will patients in these same countries be able to easily get access to a cocktail of the latest generations of monoclonal antibodies (MABs) like daratumumab and elotuzumab, immunomodulatory agents (IMIDs) like Revlimid and Pomalyst, and proteasome inihibitors (PIs) like Velcade and Kyprolis?
Alklyators, anthracylcines, etc continue to be used by some specialists in combination with novel agents with very good results. I am by no means a doctor, but I can definitely picture some specialists combining these older, tried-and-true agents with the newer generations of drugs in the coming years – and not exclusively relying on the newer generations of drugs for their treatment plans.
Don't get me wrong, I believe that there will be much better options with less side effects that will make a big difference in treating patients and improving their overall survival (OS) and QOL in the coming years – and I look forward to those improvements in treatments. But will the treatments really be based exclusively on the newer agents?
There are also many patients in many countries who are having a heck of time just getting access to the current generations of drugs available in the USA. Will patients in these same countries be able to easily get access to a cocktail of the latest generations of monoclonal antibodies (MABs) like daratumumab and elotuzumab, immunomodulatory agents (IMIDs) like Revlimid and Pomalyst, and proteasome inihibitors (PIs) like Velcade and Kyprolis?
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Lonial: Optimistic about cure for multiple myeloma
Multibilly
I agree with your thoughts exactly on this. I noted when diagnosed the relative optimism of patients and doctors here regarding the 'treatments in the pipeline' that would help to make myeloma a chronic disease. But increasingly proposed restrictions on the use of expense of cancer drugs like Revlimid and pomalidomide have 'burst the bubble' and patients are worried as to what is or is not available to them on relapse. In the UK two novel drugs are not given together as in the US and an alkylator is usually included in a triplet regime, initially at least.
The thing that I feel is missed is that looking at life expectancy data in USA and UK for myeloma for example it is similar and has been improving over the decades in both countries.This does suggest that the use of novel drugs per se may not be the driver for this. I think the intensity of and quality of monitoring, assessment and intervention in regard to more serious side affects may hold some clues.
I also like you feel that most countries outside the USA are unlikely to provide a cocktail of all the most promising types of drugs/ monoclonal antibodies. Only those with a high level of health care insurance in the USA are likely to have this. If drug companies cannot find a big enough market then what will happen?
As a slightly older person who has lived longer than many people who post on the Beacon I think the 'disposable' attitude to old things which can still be used is a modern phenomena in the age of plenty. This leads to unnecessary expenditure, to 'keep up'. New is as you note not always best or needed, but the flexibility to employ a full range of possible drug types is needed with a clonal disease.
I also do not think the approach Dr Lonial expounds will be available in the UK with a health system that is free, or to many in countries which do not use the range of drugs as are used in the USA. Genetic profiling is expensive and if drugs are not available there is little point in talking about individualised treatments to effect a 'cure', except as a research tool. This is the hard nosed fact.
I agree with your thoughts exactly on this. I noted when diagnosed the relative optimism of patients and doctors here regarding the 'treatments in the pipeline' that would help to make myeloma a chronic disease. But increasingly proposed restrictions on the use of expense of cancer drugs like Revlimid and pomalidomide have 'burst the bubble' and patients are worried as to what is or is not available to them on relapse. In the UK two novel drugs are not given together as in the US and an alkylator is usually included in a triplet regime, initially at least.
The thing that I feel is missed is that looking at life expectancy data in USA and UK for myeloma for example it is similar and has been improving over the decades in both countries.This does suggest that the use of novel drugs per se may not be the driver for this. I think the intensity of and quality of monitoring, assessment and intervention in regard to more serious side affects may hold some clues.
I also like you feel that most countries outside the USA are unlikely to provide a cocktail of all the most promising types of drugs/ monoclonal antibodies. Only those with a high level of health care insurance in the USA are likely to have this. If drug companies cannot find a big enough market then what will happen?
As a slightly older person who has lived longer than many people who post on the Beacon I think the 'disposable' attitude to old things which can still be used is a modern phenomena in the age of plenty. This leads to unnecessary expenditure, to 'keep up'. New is as you note not always best or needed, but the flexibility to employ a full range of possible drug types is needed with a clonal disease.
I also do not think the approach Dr Lonial expounds will be available in the UK with a health system that is free, or to many in countries which do not use the range of drugs as are used in the USA. Genetic profiling is expensive and if drugs are not available there is little point in talking about individualised treatments to effect a 'cure', except as a research tool. This is the hard nosed fact.
Re: Lonial: Optimistic about cure for multiple myeloma
Good morning:
Thank you for the article, RT.
I thought I would add a little to this discussion.
I have read many articles from Dr. Lonial and many interviews with him. He usually speaks very well. Because multiple myeloma is so heterogenous, he usually qualifies comments, and does not speak in absolutes. He often points out that every patient is a special case, however, he also on the other hand steps up and gives his real opinion, and is not overly obtuse. Given the fact that he was asked to prognosticate five years out, he was very circumspect with specifics in this case, I think he wanted to be general enough not to be proved wrong.
Of first note, he feels monoclonal antibodies (MABs) will be included in first line therapy. MABs are on the fast track for approval. Elotuzumab and daratumumab may be approved before the first of the year, but neither of the applications include first line therapy for now. He seems to be saying that they will very quickly be moving into first line treatment, and within five years will be universally used. In fact, there are several other MAB's in the pipeline, and they seem all to be effective enough to go through the approval process quickly (so far), and maybe there will be more than just two approved five years out.
Of second note, he did not mention dex or steroids (as included, but neither did he say that they are excluded). Although I do not recall exact details, dex does mitigate some of the problems of high dose immunomodlatory agents (IMIDs), proteasome inhibitors (PIs), and alkylators, but is given at a higher dose due to its own anti-myeloma effect. I might have a follow-on question for him as to whether or not he thinks that dex could be eliminated or reduced when optimum MAB's are brought into the triplet (or quadlet, as the case may be).
Regarding testing, he states that it will be improved, not surprisingly. His tone though, is that it will be improved by A LOT. Although I do not know specifics too well in this area, there is a ton of DNA sequencing work in medical research going on right now, for all cancer and other medical conditions. I think it may be the case that multiple myeloma testing will benefit from this, in a manner that will improve treatment decisions.
In any case, I hope he is right regarding continued quick advance of the treatments and medical tests. If you are newly diagnosed, and received your induction in the last year or two, and are fortunate enough to be on the "top" side of the curves, then you may not need your second line of treatment until four or five years from now, and the paradigm referred to by Dr. Lonial will in a sense apply to you, even if you are at first relapse, and not NDMM.
He also seems to be saying that he feels that treating to MRD- will become accepted within five years. This is also interesting. It is not universally accepted now. The concept would involve the case where you reached MRD- (and say were standard risk) in initial induction, then you may not need the ASCT. If you could not be completely induced to MRD-, then maybe you get moved to ASCT, for example. If the MRD- status proves to be a reliable of a good status of remission (I doubt it will be a perfect indicator), then it would be a good indicator of when certain treatments might be stopped, and unnecessary over-medication of patients would be reduced.
Thanks again RT for the very interesting article. Regards, JPC
Thank you for the article, RT.
I thought I would add a little to this discussion.
I have read many articles from Dr. Lonial and many interviews with him. He usually speaks very well. Because multiple myeloma is so heterogenous, he usually qualifies comments, and does not speak in absolutes. He often points out that every patient is a special case, however, he also on the other hand steps up and gives his real opinion, and is not overly obtuse. Given the fact that he was asked to prognosticate five years out, he was very circumspect with specifics in this case, I think he wanted to be general enough not to be proved wrong.
Of first note, he feels monoclonal antibodies (MABs) will be included in first line therapy. MABs are on the fast track for approval. Elotuzumab and daratumumab may be approved before the first of the year, but neither of the applications include first line therapy for now. He seems to be saying that they will very quickly be moving into first line treatment, and within five years will be universally used. In fact, there are several other MAB's in the pipeline, and they seem all to be effective enough to go through the approval process quickly (so far), and maybe there will be more than just two approved five years out.
Of second note, he did not mention dex or steroids (as included, but neither did he say that they are excluded). Although I do not recall exact details, dex does mitigate some of the problems of high dose immunomodlatory agents (IMIDs), proteasome inhibitors (PIs), and alkylators, but is given at a higher dose due to its own anti-myeloma effect. I might have a follow-on question for him as to whether or not he thinks that dex could be eliminated or reduced when optimum MAB's are brought into the triplet (or quadlet, as the case may be).
Regarding testing, he states that it will be improved, not surprisingly. His tone though, is that it will be improved by A LOT. Although I do not know specifics too well in this area, there is a ton of DNA sequencing work in medical research going on right now, for all cancer and other medical conditions. I think it may be the case that multiple myeloma testing will benefit from this, in a manner that will improve treatment decisions.
In any case, I hope he is right regarding continued quick advance of the treatments and medical tests. If you are newly diagnosed, and received your induction in the last year or two, and are fortunate enough to be on the "top" side of the curves, then you may not need your second line of treatment until four or five years from now, and the paradigm referred to by Dr. Lonial will in a sense apply to you, even if you are at first relapse, and not NDMM.
He also seems to be saying that he feels that treating to MRD- will become accepted within five years. This is also interesting. It is not universally accepted now. The concept would involve the case where you reached MRD- (and say were standard risk) in initial induction, then you may not need the ASCT. If you could not be completely induced to MRD-, then maybe you get moved to ASCT, for example. If the MRD- status proves to be a reliable of a good status of remission (I doubt it will be a perfect indicator), then it would be a good indicator of when certain treatments might be stopped, and unnecessary over-medication of patients would be reduced.
Thanks again RT for the very interesting article. Regards, JPC
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JPC - Name: JPC
Re: Lonial: Optimistic about cure for multiple myeloma
Right. So the future points to more genetic testing and using drugs which have a better success rate for your specific type of myeloma.
Seems like they are a long way from this now. I wish they would not use the word 'cure' when it carries the assumption of being on toxic drugs with side-effects forever. 'Cure' means not being on toxic drugs and the disease not advancing, and actually eliminating the source of the disease so it never comes back.
However, as an intermediate step to 'cure', increasing the efficacy of our toxic drugs would be great!
RT
Peace to all, enduring myeloma symptoms and its pharmaceutical interventions ...
Seems like they are a long way from this now. I wish they would not use the word 'cure' when it carries the assumption of being on toxic drugs with side-effects forever. 'Cure' means not being on toxic drugs and the disease not advancing, and actually eliminating the source of the disease so it never comes back.
However, as an intermediate step to 'cure', increasing the efficacy of our toxic drugs would be great!
RT
Peace to all, enduring myeloma symptoms and its pharmaceutical interventions ...
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RadiantTiger - Name: Radiant Tiger
- Who do you know with myeloma?: Myself, my deceased uncle
- When were you/they diagnosed?: Feb 2015
- Age at diagnosis: 54
Re: Lonial: Optimistic about cure for multiple myeloma
RT,
Thanks for sharing the link to Dr. Lonial's comments. Very interesting to read and think about this morning.
And it's also been fun to read the comments in this thread. Fundamentally, I agree with all of you.
But I'm not so sure I agree with Dr. Lonial on one key part of his comments. I don't think the future state he envisions will come to pass in the next 5 years.
I think Dr. Lonial's vision fits in with a range of different projects that fall in the general category of "precision medicine". It's where we are headed, but there is so much more to understand about the genetics and complicated pathways of multiple myeloma that I think five years for all of this to come to pass is way overly optimistic.
It seems to me that there is a lot of work ahead to be able to map myeloma cell RNA sequences to effective treatment strategies. And then there is the problem of clonal heterogeneity. I may be wrong here, but I expect that after 2-4 cycles of treatment, most patients will still have multiple myeloma clones. Which do you target, even of you can do the RNA sequence to treatment mapping?
I think Dr. Lonial's prediction will come true. When it does, that will be a huge advancement in the treatment of multiple myeloma. I hope we're all still around to see it!
Mike
Thanks for sharing the link to Dr. Lonial's comments. Very interesting to read and think about this morning.
And it's also been fun to read the comments in this thread. Fundamentally, I agree with all of you.
But I'm not so sure I agree with Dr. Lonial on one key part of his comments. I don't think the future state he envisions will come to pass in the next 5 years.
I think Dr. Lonial's vision fits in with a range of different projects that fall in the general category of "precision medicine". It's where we are headed, but there is so much more to understand about the genetics and complicated pathways of multiple myeloma that I think five years for all of this to come to pass is way overly optimistic.
It seems to me that there is a lot of work ahead to be able to map myeloma cell RNA sequences to effective treatment strategies. And then there is the problem of clonal heterogeneity. I may be wrong here, but I expect that after 2-4 cycles of treatment, most patients will still have multiple myeloma clones. Which do you target, even of you can do the RNA sequence to treatment mapping?
I think Dr. Lonial's prediction will come true. When it does, that will be a huge advancement in the treatment of multiple myeloma. I hope we're all still around to see it!
Mike
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mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Lonial: Optimistic about cure for multiple myeloma
Hello RT:
Excellent point. Agree with you 100% regarding the concept of "cure". Dr. Lonial did say that word in his last sentence, but I think he did say, still working towards an ultimate cure down the road, which I think agrees with your point, though you said it more definitively.
I would look at the article, however, as follows. The comments come from a research meeting. Dr. Lonial is trying to keep the research community motivated. If you are involved in research, as a doctor, a scientist, a nurse, a regulator, an investor, or a drug company, your best opiate (drug of choice) will be success. I think he is trying to keep up the excitement (or raise it) in the research community to keep the ball rolling regarding the pace of the new developments. Sometimes, you do have to be a cheerleader. I don't think his target audience in this case was necessarily the patients and the caregivers.
Best of luck to you. Rgds,
Excellent point. Agree with you 100% regarding the concept of "cure". Dr. Lonial did say that word in his last sentence, but I think he did say, still working towards an ultimate cure down the road, which I think agrees with your point, though you said it more definitively.
I would look at the article, however, as follows. The comments come from a research meeting. Dr. Lonial is trying to keep the research community motivated. If you are involved in research, as a doctor, a scientist, a nurse, a regulator, an investor, or a drug company, your best opiate (drug of choice) will be success. I think he is trying to keep up the excitement (or raise it) in the research community to keep the ball rolling regarding the pace of the new developments. Sometimes, you do have to be a cheerleader. I don't think his target audience in this case was necessarily the patients and the caregivers.
Best of luck to you. Rgds,
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JPC - Name: JPC
9 posts
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