This forum thread will be used by the Beacon Staff to post updates about the proceedings of the American Society of Hematology (ASH) meeting taking place on Day 1 (Saturday, December 10) of the conference.
Beacon forum participants are free, however, to use this thread to comment on the updates, post their own updates or thoughts, and ask questions. Everyone is encouraged to participate.
Feel free to also check out the threads dedicated to Day 2, Day 3, and Day 4 of the ASH 2011 meeting.
For an earlier discussion of ASH 2011 presentation and poster abstracts, please see this thread:
https://myelomabeacon.org/forum/ash-2011-annual-meeting-multiple-myeloma-t692.html
Forums
Re: ASH 2011 Multiple Myeloma Discussion - Day 1
Well we're off to the races!
There have been a number of pre-meeting events, but the actual ASH 2011 meeting starts today (Saturday).
And one of the sessions that kicked off the day was a 7:30 a.m. (Pacific) educational session on "Controversies and Updates in Multiple Myeloma".
Unlike most of the presentations during the meeting, an educational session is intended to be a review of what is known about a topic, rather than a discussion of brand new research results.
Thus, if you're a regular reader of The Beacon, the material presented in the educational sessions won't really cover much that is new to you.
However, if you're still climbing the "myeloma learning curve", educational sessions are a great way to familiarize yourself with key issues and concepts.
There were three presentations during this morning's educational session, and we'll cover each of them in separate postings.
There have been a number of pre-meeting events, but the actual ASH 2011 meeting starts today (Saturday).
And one of the sessions that kicked off the day was a 7:30 a.m. (Pacific) educational session on "Controversies and Updates in Multiple Myeloma".
Unlike most of the presentations during the meeting, an educational session is intended to be a review of what is known about a topic, rather than a discussion of brand new research results.
Thus, if you're a regular reader of The Beacon, the material presented in the educational sessions won't really cover much that is new to you.
However, if you're still climbing the "myeloma learning curve", educational sessions are a great way to familiarize yourself with key issues and concepts.
There were three presentations during this morning's educational session, and we'll cover each of them in separate postings.
Re: ASH 2011 Multiple Myeloma Discussion - Day 1
The first presentation during the education session was given by Dr. Donna Reece of the Princess Margaret Hospital in Toronto. The title of her presentation was "Post-Transplant Maintenance Therapy in Myeloma / Optimal Frontline Therapy."
The title of the presentation doesn't really do it justice, because the presentation actually was a solid review of a number of key concepts in the treatment of myeloma.
(Note: As a courtesy to The Beacon's readers, Dr. Reece has made the slide deck for her presentation available as a PDF file that can be downloaded and viewed. Here is the download link: http://bit.ly/vG2QB9 . )
Dr. Reece started with a discussion of how treatment of myeloma was done prior to the advent of the novel agents thalidomide, Velcade, and Revlimid. Her focus in this part of the discussion mainly was on the sort of survival outcomes that existed at that time.
She then introduced some key concepts that every myeloma patient really needs to be familiar with. Those are the concepts of induction therapy, high-dose chemotherapy followed by stem cell transplant, consolidation therapy, and maintenance therapy.
Induction therapy is the treatment that myeloma patients received after their initial diagnosis. Usually, it's four cycles of something -- where the "something" has changed over time. (More on that in a moment.)
After induction therapy, many patients (typically younger, healthier patients) go on to have their stem cells harvested, get high-dose chemotherapy (melphalan), and then have their stem cells transplanted back into their body.
What happens next with a patient in terms of treatment is an evolving issue. Dr. Reece explains that, over time, myeloma specialists have adopted the concepts of consolidation therapy and maintenance therapy which originally were used in the treatment of acute leukemia.
Maintenance therapy developed first in addition to the more conventional induction and stem cell transplant therapies. It is treatment after induction therapy (and, if relevant, after the stem cell transplant). More specifically, it is extended treatment with an anti-myeloma drug, often until a patient shows renewed signs of their disease (that is, starts to "progress" -- a horrible use of the word, when you think about it!).
A more recent kind of post-induction, post-stem cell transplant, treatment regimen is the "consolidation" regimen. Dr. Reece attributed the development of this approach to Dr. Barlogie at Arkansas.
Consolidation therapy is a relatively short round of therapy, generally intensive in nature, that takes place after a stem-cell transplant and before the start of any longer-term maintenance therapy.
After introducing these comments, Dr. Reece went on to discuss what is known about the best approach for each kind of therapy, focusing mainly on induction therapy and maintenance therapy.
She started with upfront (induction) therapy.
She noted that the evidence is very clear that upfront therapies involving at least one of the novel agents perform better than the older regimens not including a novel agent. The most extensive data that exist are for induction treatments involving a single novel agent and one or more older treatments. However, Dr. Reece believes there is increasing evidence that the most powerful induction regimens will be those involving two or more novel agents -- regimens like Revlimid plus Velcade plus dexamethasone.
That said, Dr. Reece noted that she and her colleagues typically use the so-called "CyBorD" induction regimen (cyclophosphamide plus Velcade plus dexamethasone) for most of their patients.
(For a recent Beacon summary of research related to the CyBorD induction regimen, see this article:
https://myelomabeacon.org/news/2011/12/06/initial-treatment-with-cyclophosphamide-velcade-bortezomib-and-dexamethasone-cybord-compares-favorably-in-terms-of-response-rates-and-side-effects/ )
Likewise, Dr. Reece feels the evidence that has come out recent year related to just just Revlimid combined with dexamethasone as an upfront treatment also points to the value of that combination, perhaps for specific patient populations.
(For a Beacon article on that development, follow this link:
https://myelomabeacon.org/news/2009/10/27/study-shows-higher-survival-with-revlimid-and-low-dose-dexamethasone-than-revlimid-and-high-dose-dexamethasone-in-multiple-myeloma-patients/ )
Dr. Reece turned next to the topic of maintenance therapy.
The first significant research into the potential value of maintenance therapy in myeloma involved maintenance therapy with thalidomide. Unfortunately, the results in regard to this option have been mixed.
Maintenance therapy with thalidomide has been shown rather conclusively to extend so-called "progression free survival" (how long patients maintain a stable response to their treatment, without their disease advancing). However, the impact of thalidomide maintenance therapy on overall survival has been mixed. Some studies find some improvement in overall survival, others do not.
(For a look at recent research on this subject, see this Beacon news article:
https://myelomabeacon.org/news/2011/11/02/thalidomide-maintenance-therapy-fails-to-provide-consistent-overall-survival-benefit/ )
The other issue is that thalidomide maintenance therapy can be very difficult for many patients to tolerate. The side effects of the treatment can lead many patients to discontinue treatment before their disease progresses.
Myeloma researchers also have looked at the possibility of Velcade maintenance therapy, but the research on this option is still relatively limited. Many of the so-called Velcade maintenance regimens have really been consolidation regimens, or somewhat extended consolidation regimens.
(For some Beacon articles on Velcade maintenance therapy, see this search results page:
https://myelomabeacon.org/search/Velcade+maintenance )
In contrast, there is relatively substantial research related to maintenance therapy using Revlimid. This research has shown a definite positive impact on progression-free survival. The evidence is a bit more mixed when it comes to the impact on overall survival. One major trial -- the CALGB trial -- has found an overall survival benefit to Revlimid maintenance, but the other major Revlimid maintenance trial -- the IFM trial -- has not.
One issue that has sparked concern about Revlimid maintenance therapy is the potential that it might increase a patient's risk of developing additional cancers (the so-called "secondary cancer" risk of maintenance therapy). Dr. Reece recognizes that there is this risk, but she believes it is not so significant to justify not using Revlimid as maintenance therapy.
Thus, she and her colleagues at the Princess Margaret Hospital do put most of their myeloma patients on Revlimid maintenance therapy.
(For Myeloma Beacon articles on the secondary cancer risk associated with Revlimid, see this tag page:
https://myelomabeacon.org/tag/secondary-cancer/ .)
The discussion of maintenance therapy more or less concluded Dr. Reece's presentation.
The title of the presentation doesn't really do it justice, because the presentation actually was a solid review of a number of key concepts in the treatment of myeloma.
(Note: As a courtesy to The Beacon's readers, Dr. Reece has made the slide deck for her presentation available as a PDF file that can be downloaded and viewed. Here is the download link: http://bit.ly/vG2QB9 . )
Dr. Reece started with a discussion of how treatment of myeloma was done prior to the advent of the novel agents thalidomide, Velcade, and Revlimid. Her focus in this part of the discussion mainly was on the sort of survival outcomes that existed at that time.
She then introduced some key concepts that every myeloma patient really needs to be familiar with. Those are the concepts of induction therapy, high-dose chemotherapy followed by stem cell transplant, consolidation therapy, and maintenance therapy.
Induction therapy is the treatment that myeloma patients received after their initial diagnosis. Usually, it's four cycles of something -- where the "something" has changed over time. (More on that in a moment.)
After induction therapy, many patients (typically younger, healthier patients) go on to have their stem cells harvested, get high-dose chemotherapy (melphalan), and then have their stem cells transplanted back into their body.
What happens next with a patient in terms of treatment is an evolving issue. Dr. Reece explains that, over time, myeloma specialists have adopted the concepts of consolidation therapy and maintenance therapy which originally were used in the treatment of acute leukemia.
Maintenance therapy developed first in addition to the more conventional induction and stem cell transplant therapies. It is treatment after induction therapy (and, if relevant, after the stem cell transplant). More specifically, it is extended treatment with an anti-myeloma drug, often until a patient shows renewed signs of their disease (that is, starts to "progress" -- a horrible use of the word, when you think about it!).
A more recent kind of post-induction, post-stem cell transplant, treatment regimen is the "consolidation" regimen. Dr. Reece attributed the development of this approach to Dr. Barlogie at Arkansas.
Consolidation therapy is a relatively short round of therapy, generally intensive in nature, that takes place after a stem-cell transplant and before the start of any longer-term maintenance therapy.
After introducing these comments, Dr. Reece went on to discuss what is known about the best approach for each kind of therapy, focusing mainly on induction therapy and maintenance therapy.
She started with upfront (induction) therapy.
She noted that the evidence is very clear that upfront therapies involving at least one of the novel agents perform better than the older regimens not including a novel agent. The most extensive data that exist are for induction treatments involving a single novel agent and one or more older treatments. However, Dr. Reece believes there is increasing evidence that the most powerful induction regimens will be those involving two or more novel agents -- regimens like Revlimid plus Velcade plus dexamethasone.
That said, Dr. Reece noted that she and her colleagues typically use the so-called "CyBorD" induction regimen (cyclophosphamide plus Velcade plus dexamethasone) for most of their patients.
(For a recent Beacon summary of research related to the CyBorD induction regimen, see this article:
https://myelomabeacon.org/news/2011/12/06/initial-treatment-with-cyclophosphamide-velcade-bortezomib-and-dexamethasone-cybord-compares-favorably-in-terms-of-response-rates-and-side-effects/ )
Likewise, Dr. Reece feels the evidence that has come out recent year related to just just Revlimid combined with dexamethasone as an upfront treatment also points to the value of that combination, perhaps for specific patient populations.
(For a Beacon article on that development, follow this link:
https://myelomabeacon.org/news/2009/10/27/study-shows-higher-survival-with-revlimid-and-low-dose-dexamethasone-than-revlimid-and-high-dose-dexamethasone-in-multiple-myeloma-patients/ )
Dr. Reece turned next to the topic of maintenance therapy.
The first significant research into the potential value of maintenance therapy in myeloma involved maintenance therapy with thalidomide. Unfortunately, the results in regard to this option have been mixed.
Maintenance therapy with thalidomide has been shown rather conclusively to extend so-called "progression free survival" (how long patients maintain a stable response to their treatment, without their disease advancing). However, the impact of thalidomide maintenance therapy on overall survival has been mixed. Some studies find some improvement in overall survival, others do not.
(For a look at recent research on this subject, see this Beacon news article:
https://myelomabeacon.org/news/2011/11/02/thalidomide-maintenance-therapy-fails-to-provide-consistent-overall-survival-benefit/ )
The other issue is that thalidomide maintenance therapy can be very difficult for many patients to tolerate. The side effects of the treatment can lead many patients to discontinue treatment before their disease progresses.
Myeloma researchers also have looked at the possibility of Velcade maintenance therapy, but the research on this option is still relatively limited. Many of the so-called Velcade maintenance regimens have really been consolidation regimens, or somewhat extended consolidation regimens.
(For some Beacon articles on Velcade maintenance therapy, see this search results page:
https://myelomabeacon.org/search/Velcade+maintenance )
In contrast, there is relatively substantial research related to maintenance therapy using Revlimid. This research has shown a definite positive impact on progression-free survival. The evidence is a bit more mixed when it comes to the impact on overall survival. One major trial -- the CALGB trial -- has found an overall survival benefit to Revlimid maintenance, but the other major Revlimid maintenance trial -- the IFM trial -- has not.
One issue that has sparked concern about Revlimid maintenance therapy is the potential that it might increase a patient's risk of developing additional cancers (the so-called "secondary cancer" risk of maintenance therapy). Dr. Reece recognizes that there is this risk, but she believes it is not so significant to justify not using Revlimid as maintenance therapy.
Thus, she and her colleagues at the Princess Margaret Hospital do put most of their myeloma patients on Revlimid maintenance therapy.
(For Myeloma Beacon articles on the secondary cancer risk associated with Revlimid, see this tag page:
https://myelomabeacon.org/tag/secondary-cancer/ .)
The discussion of maintenance therapy more or less concluded Dr. Reece's presentation.
Re: ASH 2011 Multiple Myeloma Discussion - Day 1
The next presentation during the educational session was by Dr. Sergio Giralt of Memorial Sloan-Kettering Cancer Center in New York City. Dr. Giralt's presentation was titled "Optimal Role For Bone Marrow Transplant."
Note: Dr. Giralt has kindly made the slides for his presentation available to The Beacon's readers. The slides are in a PDF file, which can be downloaded here: http://bit.ly/tH7DJ4 .
Dr. Giralt's presentation focused on the key question: What is the role of stem cell transplant therapy in the treatment of myeloma?
In reality, this question leads to a number of more tarrgeted questions, such as the following:
- Given the efficacy of the new myeloma treatments, do stem cell transplants still make sense ... particularly stem cell transplants soon after diagnosis?
- If we believe transplants, in general, are a good idea, should patients receive a transplant soon after diagnosis, or is it better to wait and have a transplant after initial relapse?
- What about allogeneic (donor) stem cell transplants? Should they be carried out more frequently than they are?
- What about tandem transplantation -- that is, more than one stem cell transplant, usually in relatively rapid succession? Should it be considered more frequently than it is?
Unfortunately, the data to answer these questions in not nearly as rich as, say the data that Dr. Reece was able to turn to in her discussion of induction regimens and maintenance regimens. Nevertheless, Dr. Giralt reviewed the data that are available, the trials that are ongoing, and a few interesting observations along the way.
Dr. Giralt started by admitting that he personally is strongly in favor of stem cell transplants as a treatment for multiple myeloma.
He said that, in his opinion, the current standard of care for multiple myeloma is an induction treatment involving Velcade and one or more other drugs, a stem cell transplant, and then maintenance therapy with Revlimid.
He accepts, however, that the data are not completely clear cut on whether or not a stem cell transplant should be conducted soon after diagnosis, or later in a patient's treatment.
(For two recent studies looking at this issue, see these two Beacon articles:
https://myelomabeacon.org/news/2010/12/17/early-stem-cell-transplantation-may-improve-survival-in-newly-diagnosed-multiple-myeloma-patients-ash-2010/
https://myelomabeacon.org/news/2011/10/31/study-finds-early-and-delayed-stem-cell-transplants-have-comparable-efficacy-in-newly-diagnosed-multiple-myeloma-patients/ )
More insight into the answer to this specific question is likely to come out of a trial being conducted jointly by the Dana-Farber Cancer Center in Boston and the French IFM myeloma research group.
The data also are not clear cut in regard to the role of allogeneic (donor) stem cell transplants. At first glance, it would seem that the data are not very favorable when it comes to allogeneic transplants. A study that came out at ASH last year, for example showed no benefit to an auto-allo tandem transplant treatment regimen compared to a double auto-auto transplant regimen.
(See the related Beacon article:
https://myelomabeacon.org/news/2010/12/06/donor-stem-cell-transplants-come-up-short-as-second-transplant-option-in-multiple-myeloma-patients-ash-2010/ )
However, Dr. Giralt believes approaches to allo transplantation are improving, and that researchers are, in fact, getting good results with the therapy option. So the jury is definitely still out on the issue.
Several times during his presentation, Dr. Giralt said that myeloma researchers need to think more and more about the "symptom burden" that patients experience during the treatment of multiple myeloma.
By "symptom burden", he means the results of the disease AND the treatment of the disease that reduce a patient's quality of life.
He is concerned that, as we look at treatment approaches that involve induction therapy, one or more stem cell transplants, consolidation therapy, maintenance therapy, one or more rounds of salvage therapy, and so on, that we are create a significant "symptom burden" (or "disease burden") for patients.
This needs to be taken into account as myeloma specialists think about what will be the best approach to treating myeloma patients going forward.
Likewise, Dr. Giralt feels that researchers need to start thinking more creatively about the exact way they carry out stem cell transplants and pre-stem cell transplant therapy.
He often hesitates to admit, for example, that stem cell transplants today are carried out in ways very similar to how they were carried out 15 years ago.
Likewise, although it is standard for induction therapy to consist of four cycles of "something", there is no clear rationale for why it should be four cycles. (This question was discussed in a recent exchange here in the forum. Can anyone find the exchange?)
And, in fact, a number of physicians are exploring different numbers of treatment cycles to see if different approaches make more sense.
In addition, myeloma specialists are starting to look at alternatives to high-dose melphalan prior to stem cell transplantation. Most of the alternatives being considered still involve melphalan, but alternatives are starting to be explored.
Dr. Giralt concluded his presentation by repeating that he remains convinced that stem cell transplantation provides a significant benefit to myeloma patients. But there definitely are a large number of questions that still need to be answered about this treatment option.
(Note that one of the Beacon's physician columnists, Dr. Vincent Rajkumar of the Mayo Clinic, also touched on some of the same themes covered in Dr. Giralt's presentation in a column Dr. Rajkumar wrote this summer. Here is the relevant link:
https://myelomabeacon.org/news/2011/08/05/role-of-autologous-stem-cell-transplantation-in-multiple-myeloma/ )
Note: Dr. Giralt has kindly made the slides for his presentation available to The Beacon's readers. The slides are in a PDF file, which can be downloaded here: http://bit.ly/tH7DJ4 .
Dr. Giralt's presentation focused on the key question: What is the role of stem cell transplant therapy in the treatment of myeloma?
In reality, this question leads to a number of more tarrgeted questions, such as the following:
- Given the efficacy of the new myeloma treatments, do stem cell transplants still make sense ... particularly stem cell transplants soon after diagnosis?
- If we believe transplants, in general, are a good idea, should patients receive a transplant soon after diagnosis, or is it better to wait and have a transplant after initial relapse?
- What about allogeneic (donor) stem cell transplants? Should they be carried out more frequently than they are?
- What about tandem transplantation -- that is, more than one stem cell transplant, usually in relatively rapid succession? Should it be considered more frequently than it is?
Unfortunately, the data to answer these questions in not nearly as rich as, say the data that Dr. Reece was able to turn to in her discussion of induction regimens and maintenance regimens. Nevertheless, Dr. Giralt reviewed the data that are available, the trials that are ongoing, and a few interesting observations along the way.
Dr. Giralt started by admitting that he personally is strongly in favor of stem cell transplants as a treatment for multiple myeloma.
He said that, in his opinion, the current standard of care for multiple myeloma is an induction treatment involving Velcade and one or more other drugs, a stem cell transplant, and then maintenance therapy with Revlimid.
He accepts, however, that the data are not completely clear cut on whether or not a stem cell transplant should be conducted soon after diagnosis, or later in a patient's treatment.
(For two recent studies looking at this issue, see these two Beacon articles:
https://myelomabeacon.org/news/2010/12/17/early-stem-cell-transplantation-may-improve-survival-in-newly-diagnosed-multiple-myeloma-patients-ash-2010/
https://myelomabeacon.org/news/2011/10/31/study-finds-early-and-delayed-stem-cell-transplants-have-comparable-efficacy-in-newly-diagnosed-multiple-myeloma-patients/ )
More insight into the answer to this specific question is likely to come out of a trial being conducted jointly by the Dana-Farber Cancer Center in Boston and the French IFM myeloma research group.
The data also are not clear cut in regard to the role of allogeneic (donor) stem cell transplants. At first glance, it would seem that the data are not very favorable when it comes to allogeneic transplants. A study that came out at ASH last year, for example showed no benefit to an auto-allo tandem transplant treatment regimen compared to a double auto-auto transplant regimen.
(See the related Beacon article:
https://myelomabeacon.org/news/2010/12/06/donor-stem-cell-transplants-come-up-short-as-second-transplant-option-in-multiple-myeloma-patients-ash-2010/ )
However, Dr. Giralt believes approaches to allo transplantation are improving, and that researchers are, in fact, getting good results with the therapy option. So the jury is definitely still out on the issue.
Several times during his presentation, Dr. Giralt said that myeloma researchers need to think more and more about the "symptom burden" that patients experience during the treatment of multiple myeloma.
By "symptom burden", he means the results of the disease AND the treatment of the disease that reduce a patient's quality of life.
He is concerned that, as we look at treatment approaches that involve induction therapy, one or more stem cell transplants, consolidation therapy, maintenance therapy, one or more rounds of salvage therapy, and so on, that we are create a significant "symptom burden" (or "disease burden") for patients.
This needs to be taken into account as myeloma specialists think about what will be the best approach to treating myeloma patients going forward.
Likewise, Dr. Giralt feels that researchers need to start thinking more creatively about the exact way they carry out stem cell transplants and pre-stem cell transplant therapy.
He often hesitates to admit, for example, that stem cell transplants today are carried out in ways very similar to how they were carried out 15 years ago.
Likewise, although it is standard for induction therapy to consist of four cycles of "something", there is no clear rationale for why it should be four cycles. (This question was discussed in a recent exchange here in the forum. Can anyone find the exchange?)
And, in fact, a number of physicians are exploring different numbers of treatment cycles to see if different approaches make more sense.
In addition, myeloma specialists are starting to look at alternatives to high-dose melphalan prior to stem cell transplantation. Most of the alternatives being considered still involve melphalan, but alternatives are starting to be explored.
Dr. Giralt concluded his presentation by repeating that he remains convinced that stem cell transplantation provides a significant benefit to myeloma patients. But there definitely are a large number of questions that still need to be answered about this treatment option.
(Note that one of the Beacon's physician columnists, Dr. Vincent Rajkumar of the Mayo Clinic, also touched on some of the same themes covered in Dr. Giralt's presentation in a column Dr. Rajkumar wrote this summer. Here is the relevant link:
https://myelomabeacon.org/news/2011/08/05/role-of-autologous-stem-cell-transplantation-in-multiple-myeloma/ )
Re: ASH 2011 Multiple Myeloma Discussion - Day 1
The final presentation of the educational session was by Dr. Kenneth Anderson of the Dana-Farber Cancer Center in Boston. Dr. Anderson's presentation was titled "New Insights Into Therapeutic Targets In Myeloma."
The presentation was a very useful summary of the many different approaches myeloma specialists are exploring to come up with new treatments for the disease. The presentation was rather technical at times, as Dr. Anderson typically explained the biological and biochemical basis for many of the new treatments.
But the clear message that came through during the presentation was that there are many, many new drugs being explored as potential new treatments for multiple myeloma.
Dr. Anderson organized his presentation by grouping the new treatments he discussed by how they work. Thus, he spoke first about drugs that involve genetically engineered antibodies (proteins typically used by the body to defend itself infection).
There are several antibody-based treatments under development for myeloma, but the one that is probably the furthest along is elotuzumab. It has been found to be active in relapsed myeloma when combined with Revlimid, with response rates often as high as 80 or 90 percent.
(For more on elotuzumab: https://myelomabeacon.org/tag/elotuzumab )
Another antibody-based treatment that Dr. Anderson highlighted is the drug BT062. It is actually a combination treatment, with an antibody chemically connected to several other anti-myeloma agents.
A second key group of new treatments that Dr. Anderson highlighted is newer generation proteasome inhibitors. Velcade was the first anti-myeloma agent in the proteasome inhibitor class. Carfilzomib is another proteasome inhibitor that has shown strong efficacy and safety. The company developing carfilzomib already has asked the U.S. Food and Drug Administration to approve carfilzomib as a new treatment for myleoma.
(For all Beacon news articles related to carfilzomib, see https://myelomabeacon.org/tag/carfilzomib .)
But there are other proteasome inhibitors under development. For example, a proteasome inhibitor that can be taken as a pill or capsule, MLN2238/9708, is being developed by the company that originally developed Velcade (Millennium), and the proteasome inhibitor NPI-0092 also is showing promise in early stage clinical trials.
The original "novel" myeloma therapies were thalidomide, Velcade, and Revlimid. Revlimid and thalidomide are chemical cousins that belong to a class of drugs often called "imids", or immummodulatory therapies.
Just as there are new proteasome inhibitors like Velcade under development as new myeloma treatments, there is a new imid under development -- pomalidomide. Dr. Anderson discussed the biological rationale for pomalidomide and summarized data showing pomalidomide's promising efficacy in relapsed myeloma patients. (For more Beacon articles on pomalidomide, see https://myelomabeacon.org/tag/pomalidomide .)
One might think at this point that there couldn't possibly be additional classes of potential new myeloma treatments under development. However, Dr. Anderson went on to mention five to ten further classes of treatments with anti-myeloma drugs being researched.
He spoke somewhat at length, for example, about the anti-DKK1 treatment BHQ880 and the anti-BAFF agent LY2127399.
But he also went on to list other promising classes of treatments, such as Akt inhibitors (e.g., perifosine), HDAC inhibitors (panobinostat, Zolinza (vorinostat), romidepsin), kinesis spindle protein inhibitors, cyclin dependent kinase inhibitors, hedgehog pathway inhibitors (BMS833923), and MEK inhibitors (selumetinib / AZD6244).
Given all these potential treatments, Dr. Anderson remains confident that the treatment of myeloma will continue to evolve so that, for more and more patients, the disease will become a chronic condition rather than the incurable cancer it was 20 years ago.
(Dr. Anderson also discussed potential new treatments for myeloma in an interview he did with The Myeloma Beacon, published earlier this year. Here is a link to that interview:
https://myelomabeacon.org/news/2011/02/28/thought-leader-perspective-dr-kenneth-anderson-on-the-future-of-multiple-myeloma-treatment/ .)
The presentation was a very useful summary of the many different approaches myeloma specialists are exploring to come up with new treatments for the disease. The presentation was rather technical at times, as Dr. Anderson typically explained the biological and biochemical basis for many of the new treatments.
But the clear message that came through during the presentation was that there are many, many new drugs being explored as potential new treatments for multiple myeloma.
Dr. Anderson organized his presentation by grouping the new treatments he discussed by how they work. Thus, he spoke first about drugs that involve genetically engineered antibodies (proteins typically used by the body to defend itself infection).
There are several antibody-based treatments under development for myeloma, but the one that is probably the furthest along is elotuzumab. It has been found to be active in relapsed myeloma when combined with Revlimid, with response rates often as high as 80 or 90 percent.
(For more on elotuzumab: https://myelomabeacon.org/tag/elotuzumab )
Another antibody-based treatment that Dr. Anderson highlighted is the drug BT062. It is actually a combination treatment, with an antibody chemically connected to several other anti-myeloma agents.
A second key group of new treatments that Dr. Anderson highlighted is newer generation proteasome inhibitors. Velcade was the first anti-myeloma agent in the proteasome inhibitor class. Carfilzomib is another proteasome inhibitor that has shown strong efficacy and safety. The company developing carfilzomib already has asked the U.S. Food and Drug Administration to approve carfilzomib as a new treatment for myleoma.
(For all Beacon news articles related to carfilzomib, see https://myelomabeacon.org/tag/carfilzomib .)
But there are other proteasome inhibitors under development. For example, a proteasome inhibitor that can be taken as a pill or capsule, MLN2238/9708, is being developed by the company that originally developed Velcade (Millennium), and the proteasome inhibitor NPI-0092 also is showing promise in early stage clinical trials.
The original "novel" myeloma therapies were thalidomide, Velcade, and Revlimid. Revlimid and thalidomide are chemical cousins that belong to a class of drugs often called "imids", or immummodulatory therapies.
Just as there are new proteasome inhibitors like Velcade under development as new myeloma treatments, there is a new imid under development -- pomalidomide. Dr. Anderson discussed the biological rationale for pomalidomide and summarized data showing pomalidomide's promising efficacy in relapsed myeloma patients. (For more Beacon articles on pomalidomide, see https://myelomabeacon.org/tag/pomalidomide .)
One might think at this point that there couldn't possibly be additional classes of potential new myeloma treatments under development. However, Dr. Anderson went on to mention five to ten further classes of treatments with anti-myeloma drugs being researched.
He spoke somewhat at length, for example, about the anti-DKK1 treatment BHQ880 and the anti-BAFF agent LY2127399.
But he also went on to list other promising classes of treatments, such as Akt inhibitors (e.g., perifosine), HDAC inhibitors (panobinostat, Zolinza (vorinostat), romidepsin), kinesis spindle protein inhibitors, cyclin dependent kinase inhibitors, hedgehog pathway inhibitors (BMS833923), and MEK inhibitors (selumetinib / AZD6244).
Given all these potential treatments, Dr. Anderson remains confident that the treatment of myeloma will continue to evolve so that, for more and more patients, the disease will become a chronic condition rather than the incurable cancer it was 20 years ago.
(Dr. Anderson also discussed potential new treatments for myeloma in an interview he did with The Myeloma Beacon, published earlier this year. Here is a link to that interview:
https://myelomabeacon.org/news/2011/02/28/thought-leader-perspective-dr-kenneth-anderson-on-the-future-of-multiple-myeloma-treatment/ .)
Re: ASH 2011 Multiple Myeloma Discussion - Day 1
There were no further oral presentations during the rest of the day today. Instead, the new myeloma research was presented in the form of posters -- lots of posters!
So the Myeloma Beacon team spent the rest of today working through the posters, deciding which ones deserved highlighting here in the forum, and -- where possible -- we also grouped them together a bit by common theme.
We'll start with the review of the posters by discussing the ones that deal with potential new treatments for myeloma.
There were two agents covered by posters today that we have not heard too much about in the past.
One is a drug being developed by GlaxoSmithKline, codenamed GSK2110183. It is a so-called "Akt inhibitor", which means it is in the same class of drugs as perifosine, another potential myeloma drug that is further along in development. Both GSK2110183 and perifosine are oral drugs, meaning they will be able to be taken as pills or capsules, rather than by injection or infusion.
The other relatively new drug covered in a poster presentation -- and which we haven't heard too much about in the past -- was ARRY-520, which is being developed by Array BioPharma. ARRY-520 is in a new class of potential anti-myeloma agents known as kinesin spindle protein inhibitors. It is administered by infusion.
Both GSK2110183 and ARRY-520 were tested as single treatments for myeloma patients who have failed previous therapies. In fact, in most cases, the patients had failed a substantial number of previous therapies -- a median of 5 previous therapies in the GSK2110183 trial and 6 previous therapies in the ARRY-520 trial.
The data for GSK2110183 is from a Phase 1 study that started out with patients from a number of blood cancers, not just myeloma. A total of 73 patients were included in the study, 34 of whom had myeloma. The trial mainly was designed to find the best dose for the drug, which was determined to be 125 mg. This dose was then tested further on the myeloma patients, and 3 (8.8%) of the patients achieved a partial response and another 3 (8.8%) a minimal response. (We'll put these numbers in perspective later in this posting.) The most common side effects were gastrointestinal in nature, such as nausea (20%) or diarrhea (16%). Side effects having to do with blood cell levels -- such as anemia or low white blood cell levels -- were not observed in many myeloma patients.
The data for ARRY-520 is also from a Phase 1 study focused on determining the best dosing for the drug. Some of the patients in the study also received granulocyte colony-stimulating factor (GCSF, sold in the U.S. under the brand names Neupogen or Neulasta), which counteracts the tendency of ARRY-520 to lower white blood cell counts.
This trial of the drug has collected and evaluated data on 30 patients. Of those patients, 3 patients (10%) achieved a partial response, 1 patient (3.3%) achieved a minor response, and 8 patients (27 percent) achieved stable disease lasting more than six months.
The patients experiencing a partial response had a median duration of response that was greater than 8 months. The median time to partial response was long -- 7.2 months.
How do the response rates for GSK2110183 and ARRY-520 compare to data for other drugs that have been tested in relapsed myeloma patients?
Well, the potential new myeloma drug carfilzomib, which many myeloma specialists consider to be rather promising, was tested as a single treatment for relapsed myeloma patients who had received a median of four previous therapies.
In the carfilzomib trial, which had over 200 patients, 24 percent of the patients achieved a partial response or better, and another 10 percent achieved a minimal response.
Thus, the response rates for GSK2110183 and ARRY-520 look reasonable, but they do not match the rates seen for carfilzomib when it was tested in relapsed / refractory myeloma patients.
And, in fact, the abstract for the GSK2110183 poster concludes: "Further work is ongoing to identify the patients who are most likely to respond to [GSK2110183], as well as to define the most rational combination of [GSK2110183] with other agents in order to maximize the clinical benefit for multiple myeloma patients."
In contrast, the authors of the ARRY-520 poster indicate that it will be tested further in a Phase 2 trial, using a dose of 1.5 mg/m2/day in combination with GCSF.
The abstract for the GSK2110183 poster is viewable online here:
http://ash.confex.com/ash/2011/webprogram/Paper38196.html
The abstract for the ARRY-520 poster is viewable online here:
http://ash.confex.com/ash/2011/webprogram/Paper41766.html
For more on the carfilzomib trial involving relapsed myeloma patient, see the second half of the following The Myeloma Beacon article:
https://myelomabeacon.org/news/2010/12/20/carfilzomib-shows-promise-in-both-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-patients-ash-2010/
So the Myeloma Beacon team spent the rest of today working through the posters, deciding which ones deserved highlighting here in the forum, and -- where possible -- we also grouped them together a bit by common theme.
We'll start with the review of the posters by discussing the ones that deal with potential new treatments for myeloma.
There were two agents covered by posters today that we have not heard too much about in the past.
One is a drug being developed by GlaxoSmithKline, codenamed GSK2110183. It is a so-called "Akt inhibitor", which means it is in the same class of drugs as perifosine, another potential myeloma drug that is further along in development. Both GSK2110183 and perifosine are oral drugs, meaning they will be able to be taken as pills or capsules, rather than by injection or infusion.
The other relatively new drug covered in a poster presentation -- and which we haven't heard too much about in the past -- was ARRY-520, which is being developed by Array BioPharma. ARRY-520 is in a new class of potential anti-myeloma agents known as kinesin spindle protein inhibitors. It is administered by infusion.
Both GSK2110183 and ARRY-520 were tested as single treatments for myeloma patients who have failed previous therapies. In fact, in most cases, the patients had failed a substantial number of previous therapies -- a median of 5 previous therapies in the GSK2110183 trial and 6 previous therapies in the ARRY-520 trial.
The data for GSK2110183 is from a Phase 1 study that started out with patients from a number of blood cancers, not just myeloma. A total of 73 patients were included in the study, 34 of whom had myeloma. The trial mainly was designed to find the best dose for the drug, which was determined to be 125 mg. This dose was then tested further on the myeloma patients, and 3 (8.8%) of the patients achieved a partial response and another 3 (8.8%) a minimal response. (We'll put these numbers in perspective later in this posting.) The most common side effects were gastrointestinal in nature, such as nausea (20%) or diarrhea (16%). Side effects having to do with blood cell levels -- such as anemia or low white blood cell levels -- were not observed in many myeloma patients.
The data for ARRY-520 is also from a Phase 1 study focused on determining the best dosing for the drug. Some of the patients in the study also received granulocyte colony-stimulating factor (GCSF, sold in the U.S. under the brand names Neupogen or Neulasta), which counteracts the tendency of ARRY-520 to lower white blood cell counts.
This trial of the drug has collected and evaluated data on 30 patients. Of those patients, 3 patients (10%) achieved a partial response, 1 patient (3.3%) achieved a minor response, and 8 patients (27 percent) achieved stable disease lasting more than six months.
The patients experiencing a partial response had a median duration of response that was greater than 8 months. The median time to partial response was long -- 7.2 months.
How do the response rates for GSK2110183 and ARRY-520 compare to data for other drugs that have been tested in relapsed myeloma patients?
Well, the potential new myeloma drug carfilzomib, which many myeloma specialists consider to be rather promising, was tested as a single treatment for relapsed myeloma patients who had received a median of four previous therapies.
In the carfilzomib trial, which had over 200 patients, 24 percent of the patients achieved a partial response or better, and another 10 percent achieved a minimal response.
Thus, the response rates for GSK2110183 and ARRY-520 look reasonable, but they do not match the rates seen for carfilzomib when it was tested in relapsed / refractory myeloma patients.
And, in fact, the abstract for the GSK2110183 poster concludes: "Further work is ongoing to identify the patients who are most likely to respond to [GSK2110183], as well as to define the most rational combination of [GSK2110183] with other agents in order to maximize the clinical benefit for multiple myeloma patients."
In contrast, the authors of the ARRY-520 poster indicate that it will be tested further in a Phase 2 trial, using a dose of 1.5 mg/m2/day in combination with GCSF.
The abstract for the GSK2110183 poster is viewable online here:
http://ash.confex.com/ash/2011/webprogram/Paper38196.html
The abstract for the ARRY-520 poster is viewable online here:
http://ash.confex.com/ash/2011/webprogram/Paper41766.html
For more on the carfilzomib trial involving relapsed myeloma patient, see the second half of the following The Myeloma Beacon article:
https://myelomabeacon.org/news/2010/12/20/carfilzomib-shows-promise-in-both-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-patients-ash-2010/
Re: ASH 2011 Multiple Myeloma Discussion - Day 1
Speaking of carfilzomib when it is used as a treatment for relapsed myeloma patients, there was a poster today with a long, but promising, title:
"Unfavorable Cytogenetic Characteristics Do Not Adversely Impact Response Rates in Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Single-Agent Carfilzomib on the 003 (A1) Study"
The title suggests that carfilzomib, when used in relapsed patients, may have the same benefit regardless of whether patients have so-called "high risk" genetic characteristics.
The results of the study, however, are not quite as compelling as the title makes them out to be.
It is true that, when the relapsed myeloma patients in the carfilzomib study covered by the poster are split into two groups -- those without "high-risk" genetic characteristics, and those with such characteristics -- carfilzomib's overall response rate is actually higher (30 percent) than it is in patients without the high risk genetic characteristics (23 percent).
However, in the case of other key outcome measures, the trend is consistently in the direction of carfilzomib performing worse in patients with high-risk genetic characteristics.
This can be seen by looking at some key statistics, with the data for patients without high-risk genetic characteristics first, followed by data for "high-risk" patients:
Median duration of response: 8.3 months, 6.9 months
Median time to progression: 4.6 months, 3.9 months
Median overall survival: 19.2 months, 11.9 months
The difference in overall survival times appears to be statistically significant, although the study authors do not address the point directly. Differences in the other results are not statistically significant.
Thus, although carfilzomib seems to do rather well in high-risk relapsed myeloma patients, it's not clear that it does as well as suggested by the title of author's poster and abstract.
Here is a link to the poster's abstract.
http://ash.confex.com/ash/2011/webprogram/Paper39224.html
Note that the data quoted above are from the poster as it was presented today at the ASH meeting
"Unfavorable Cytogenetic Characteristics Do Not Adversely Impact Response Rates in Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Single-Agent Carfilzomib on the 003 (A1) Study"
The title suggests that carfilzomib, when used in relapsed patients, may have the same benefit regardless of whether patients have so-called "high risk" genetic characteristics.
The results of the study, however, are not quite as compelling as the title makes them out to be.
It is true that, when the relapsed myeloma patients in the carfilzomib study covered by the poster are split into two groups -- those without "high-risk" genetic characteristics, and those with such characteristics -- carfilzomib's overall response rate is actually higher (30 percent) than it is in patients without the high risk genetic characteristics (23 percent).
However, in the case of other key outcome measures, the trend is consistently in the direction of carfilzomib performing worse in patients with high-risk genetic characteristics.
This can be seen by looking at some key statistics, with the data for patients without high-risk genetic characteristics first, followed by data for "high-risk" patients:
Median duration of response: 8.3 months, 6.9 months
Median time to progression: 4.6 months, 3.9 months
Median overall survival: 19.2 months, 11.9 months
The difference in overall survival times appears to be statistically significant, although the study authors do not address the point directly. Differences in the other results are not statistically significant.
Thus, although carfilzomib seems to do rather well in high-risk relapsed myeloma patients, it's not clear that it does as well as suggested by the title of author's poster and abstract.
Here is a link to the poster's abstract.
http://ash.confex.com/ash/2011/webprogram/Paper39224.html
Note that the data quoted above are from the poster as it was presented today at the ASH meeting
Re: ASH 2011 Multiple Myeloma Discussion - Day 1
Let's take a break for a while from the today's poster's dealing with new myeloma drug therapies and turn to another important topic: stem cell transplants.
At the educational session that kicked off the day, Dr. Sergio Giralt commented that the basic approach to autologous stem cell transplantation hasn't changed much in about 15 years.
Well, there were two poster's today that discussed some potential variations on the standard approach to stem cell transplantation.
One very interesting poster was from researchers at Duke University in Durham, North Carolina. They made use of the fact that, in the late 1990s and early 2000s, physicians at Duke gave myeloma patients a combined chemotherapy ("conditioning") regimen of high dose melphalan and BCNU (Carmustine) at 500 mg/m2.
Then, when novel agents for the treatment of myeloma starting being introduced, the Duke physicians switched to using only high dose melphalan as the conditioning regimen immediately prior to stem cell transplantation.
So the Duke researchers decided to look at what happened to these two groups of myeloma patients -- those treated with both melphalan and BCNU prior to stem cell transplant, and those treated with only melphalan prior to transplant.
What the researchers found was that there clearly is a benefit to the melphalan+BCNU combination. The benefit is not yet statistically significant when the focus is on overall survival, although there definitely is a trend to better survival for the combination regimen.
Furthermore, there is a statistically significant advantage to the combined melphala+BCNU regimen when looking at a measure similar to the commonly used "progression free survival" metric.
The survival benefits for the combination regimen are particularly interesting when one recalls that the patients treated with this regimen typically were not receiving any novel agents as part of their upfront (induction) therapy. In comparison, the patients who received only high dose melphalan prior to stem cell transplant probably were being treated quite often with a novel agent during their induction therapy.
Thus, the Duke researchers believe the combination regimen of melphalan+BCNU deserves further investigation
The abstract for the Duke poster is online at:
http://ash.confex.com/ash/2011/webprogram/Paper39855.html
There may be an alternative, however, to the BCNU+melphalan combination. Researchers from Cornell University's medical school presented a poster today that looks at a Phase 1 study that combines Treanda (bendamustine) with melphalan as a conditioning regimen prior to autologous stem cell transplant.
The Cornell study doesn't have any data comparing Treanda+melphalan versus melphalan alone. Remember, Phase 1 studies typically focus on determining the safe dose for a drug. And this study was no different. It looked at a number of different Treanda doses to combine with high-dose melphalan therapy.
The results of the trial were sufficiently convincing, however, in terms of the safety and efficacy of the combination that it will be tested further in a Phase 2 trial, which is already ongoing.
The abstract for this study can be found online at:
http://ash.confex.com/ash/2011/webprogram/Paper41809.html
At the educational session that kicked off the day, Dr. Sergio Giralt commented that the basic approach to autologous stem cell transplantation hasn't changed much in about 15 years.
Well, there were two poster's today that discussed some potential variations on the standard approach to stem cell transplantation.
One very interesting poster was from researchers at Duke University in Durham, North Carolina. They made use of the fact that, in the late 1990s and early 2000s, physicians at Duke gave myeloma patients a combined chemotherapy ("conditioning") regimen of high dose melphalan and BCNU (Carmustine) at 500 mg/m2.
Then, when novel agents for the treatment of myeloma starting being introduced, the Duke physicians switched to using only high dose melphalan as the conditioning regimen immediately prior to stem cell transplantation.
So the Duke researchers decided to look at what happened to these two groups of myeloma patients -- those treated with both melphalan and BCNU prior to stem cell transplant, and those treated with only melphalan prior to transplant.
What the researchers found was that there clearly is a benefit to the melphalan+BCNU combination. The benefit is not yet statistically significant when the focus is on overall survival, although there definitely is a trend to better survival for the combination regimen.
Furthermore, there is a statistically significant advantage to the combined melphala+BCNU regimen when looking at a measure similar to the commonly used "progression free survival" metric.
The survival benefits for the combination regimen are particularly interesting when one recalls that the patients treated with this regimen typically were not receiving any novel agents as part of their upfront (induction) therapy. In comparison, the patients who received only high dose melphalan prior to stem cell transplant probably were being treated quite often with a novel agent during their induction therapy.
Thus, the Duke researchers believe the combination regimen of melphalan+BCNU deserves further investigation
The abstract for the Duke poster is online at:
http://ash.confex.com/ash/2011/webprogram/Paper39855.html
There may be an alternative, however, to the BCNU+melphalan combination. Researchers from Cornell University's medical school presented a poster today that looks at a Phase 1 study that combines Treanda (bendamustine) with melphalan as a conditioning regimen prior to autologous stem cell transplant.
The Cornell study doesn't have any data comparing Treanda+melphalan versus melphalan alone. Remember, Phase 1 studies typically focus on determining the safe dose for a drug. And this study was no different. It looked at a number of different Treanda doses to combine with high-dose melphalan therapy.
The results of the trial were sufficiently convincing, however, in terms of the safety and efficacy of the combination that it will be tested further in a Phase 2 trial, which is already ongoing.
The abstract for this study can be found online at:
http://ash.confex.com/ash/2011/webprogram/Paper41809.html
Re: ASH 2011 Multiple Myeloma Discussion - Day 1
Now for some odds and ends ...
There was a poster by German researchers that looked at whole body MRI results and what they indicate about a myeloma patient's prognosis.
The researchers note that it is widely accepted that the number of bone lesions a patient has when he or she is first diagnosed with myeloma is a indicator of the patient's prognosis. The more bone lesions a patient has, the worse their prognosis.
What the researchers of today's poster look at, using whole body MRI, is whether there also is a correlation between prognosis and the number of bone lesions detected after a patient has had a stem cell transplant. They find that there is a correlation, and it remains negative: patients who have more bone lesions detected after stem cell transplant have a poorer prognosis than other patients.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper43208.html
A much-discussed topic in the myeloma community this past year has been secondary cancers and whether, in particular, maintenance therapy with Revlimid leads to higher rates of secondary cancer in myeloma patients.
Not surprisingly, there are several posters and presentations on this topic at this year's ASH meeting.
One of those posters was presented today. It summarized the results of an analysis by researchers from the Gundersen Lutheran Health System in Wisconsin.
The poster authors looked at the incidence of secondary cancers in U.S. myeloma patients as recorded in the so-called "SEER Database". This is the main database of U.S. cancer patients used to measure things like how often certain cancers occur and how long patients with different cancers live after they've been diagnosed.
The researchers looked at data in the SEER database for the years 1973 to 2008. They split the data into 5 time periods:
1. Before January 2000 (control),
2. January 2000-April 2003 (off-label thalidomide)
3. May 2003-April 2006 (Velcade approval)
4. May 2006-September 2006 (thalidomide approval)
5. October 2006-December 2008 (Revlimid approval).
Then, for each time period, they measured what share of myeloma patients diagnosed in those years developed a secondary cancer with two years of their myeloma diagnosis.
The researchers found that rates of secondary cancer among myeloma patients increased in periods 2 through 5 compared to what they were in the first (control) period.
By the fourth and fifth periods, the odds of myeloma patients getting a secondary cancer were 53-63 percent higher than they were in the period before January 2000.
The authors recognize that their analysis has limitations. For example, the analysis does not make use of any data about how many myeloma patients in the different time periods were getting stem cell transplants.
This is potentially important since some researchers believe that Revlimid's impact on a patient's risk for developing a secondary cancer could depend on whether or not the patient has received a stem cell transplant.
Nevertheless, the authors believe their results are further evidence of a potential link between the use of novel myeloma treatments and an increased risk of secondary cancer.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper44811.html
Another development that has gotten a lot of attention during the past year has been the growing use of Velcade administered subcutaneously, rather than intravenously.
The growing use of "subq" Velcade, as it is often called, has been based on some published research showing that the efficacy of subcutaneous Velcade is equivalent to IV Velcade, but the side effects are not as extensive
A poster during today's ASH session provided some evidence as to why the two ways of administering might result in similar efficacy but improved side effects for the subcutaneous option.
The poster reported an analysis of patients who participated in trials involving both subcutaneous and intravenous Velcade. The patients allowed their blood to be tested during regular intervals after Velcade administering, and researchers then measured the concentration of Velcade in the patients' blood samples.
The researchers found that the overall concentration of Velcade over time was similar between the two ways of administering the drug. This most likely accounts for the similar efficacy of the two ways of giving the drug.
However, the concentration of Velcade in the blood did not spike nearly as much when the drug is administered subcutaneously, and the drug also persists somewhat longer in the blood after subcutaneous administration.
This difference between the two ways of giving the drug could explain the different side effects associated with the two approaches to giving the drug if especially high peak concentrations of the drug play an important role in the development of side effects such as peripheral neuropathy.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper38093.html
Beacon article with detailed information on subcutaneous Velcade:
https://myelomabeacon.org/news/2011/09/02/subcutaneous-velcade-bortezomib-information-for-multiple-myeloma-patients/
Finally, a poster by researchers at Emory University in Atlanta reviewed the key studies that have looked into using thalidomide as maintenance therapy.
As Dr. Donna Reece noted earlier in the day during the educational session, when researchers have compared thalidomide maintenance therapy to the option of patients not taking maintenance therapy at all, the result consistently has been that there is a benefit to thalidomide maintenance therapy in terms of "progression free survival" -- that is, delaying the time when patients relapse.
However, there have been mixed results in regard to whether or not thalidomide maintenance therapy extends the overall survival of patients. Some studies have shown a survival benefit. Others have not.
In their "meta analysis" (or combined analysis), the Emory researchers find, once again, convincing evidence that thalidomide maintenance extends progression free survival.
However, they also find that, taking into account all the studies, there is a statistically significant benefit to thalidomide in terms of overall survival.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper44634.html
There was a poster by German researchers that looked at whole body MRI results and what they indicate about a myeloma patient's prognosis.
The researchers note that it is widely accepted that the number of bone lesions a patient has when he or she is first diagnosed with myeloma is a indicator of the patient's prognosis. The more bone lesions a patient has, the worse their prognosis.
What the researchers of today's poster look at, using whole body MRI, is whether there also is a correlation between prognosis and the number of bone lesions detected after a patient has had a stem cell transplant. They find that there is a correlation, and it remains negative: patients who have more bone lesions detected after stem cell transplant have a poorer prognosis than other patients.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper43208.html
A much-discussed topic in the myeloma community this past year has been secondary cancers and whether, in particular, maintenance therapy with Revlimid leads to higher rates of secondary cancer in myeloma patients.
Not surprisingly, there are several posters and presentations on this topic at this year's ASH meeting.
One of those posters was presented today. It summarized the results of an analysis by researchers from the Gundersen Lutheran Health System in Wisconsin.
The poster authors looked at the incidence of secondary cancers in U.S. myeloma patients as recorded in the so-called "SEER Database". This is the main database of U.S. cancer patients used to measure things like how often certain cancers occur and how long patients with different cancers live after they've been diagnosed.
The researchers looked at data in the SEER database for the years 1973 to 2008. They split the data into 5 time periods:
1. Before January 2000 (control),
2. January 2000-April 2003 (off-label thalidomide)
3. May 2003-April 2006 (Velcade approval)
4. May 2006-September 2006 (thalidomide approval)
5. October 2006-December 2008 (Revlimid approval).
Then, for each time period, they measured what share of myeloma patients diagnosed in those years developed a secondary cancer with two years of their myeloma diagnosis.
The researchers found that rates of secondary cancer among myeloma patients increased in periods 2 through 5 compared to what they were in the first (control) period.
By the fourth and fifth periods, the odds of myeloma patients getting a secondary cancer were 53-63 percent higher than they were in the period before January 2000.
The authors recognize that their analysis has limitations. For example, the analysis does not make use of any data about how many myeloma patients in the different time periods were getting stem cell transplants.
This is potentially important since some researchers believe that Revlimid's impact on a patient's risk for developing a secondary cancer could depend on whether or not the patient has received a stem cell transplant.
Nevertheless, the authors believe their results are further evidence of a potential link between the use of novel myeloma treatments and an increased risk of secondary cancer.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper44811.html
Another development that has gotten a lot of attention during the past year has been the growing use of Velcade administered subcutaneously, rather than intravenously.
The growing use of "subq" Velcade, as it is often called, has been based on some published research showing that the efficacy of subcutaneous Velcade is equivalent to IV Velcade, but the side effects are not as extensive
A poster during today's ASH session provided some evidence as to why the two ways of administering might result in similar efficacy but improved side effects for the subcutaneous option.
The poster reported an analysis of patients who participated in trials involving both subcutaneous and intravenous Velcade. The patients allowed their blood to be tested during regular intervals after Velcade administering, and researchers then measured the concentration of Velcade in the patients' blood samples.
The researchers found that the overall concentration of Velcade over time was similar between the two ways of administering the drug. This most likely accounts for the similar efficacy of the two ways of giving the drug.
However, the concentration of Velcade in the blood did not spike nearly as much when the drug is administered subcutaneously, and the drug also persists somewhat longer in the blood after subcutaneous administration.
This difference between the two ways of giving the drug could explain the different side effects associated with the two approaches to giving the drug if especially high peak concentrations of the drug play an important role in the development of side effects such as peripheral neuropathy.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper38093.html
Beacon article with detailed information on subcutaneous Velcade:
https://myelomabeacon.org/news/2011/09/02/subcutaneous-velcade-bortezomib-information-for-multiple-myeloma-patients/
Finally, a poster by researchers at Emory University in Atlanta reviewed the key studies that have looked into using thalidomide as maintenance therapy.
As Dr. Donna Reece noted earlier in the day during the educational session, when researchers have compared thalidomide maintenance therapy to the option of patients not taking maintenance therapy at all, the result consistently has been that there is a benefit to thalidomide maintenance therapy in terms of "progression free survival" -- that is, delaying the time when patients relapse.
However, there have been mixed results in regard to whether or not thalidomide maintenance therapy extends the overall survival of patients. Some studies have shown a survival benefit. Others have not.
In their "meta analysis" (or combined analysis), the Emory researchers find, once again, convincing evidence that thalidomide maintenance extends progression free survival.
However, they also find that, taking into account all the studies, there is a statistically significant benefit to thalidomide in terms of overall survival.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper44634.html
Re: ASH 2011 Multiple Myeloma Discussion - Day 1
The last poster we'd like to speak about from Saturday's session concerns allogeneic (donor) stem cell transplantation.
As most Beacon readers know, allogeneic stem cell transplantation is a potentially curative therapy for myeloma. However, up until recently, it has not been carried out frequently on myeloma patients -- particularly newly diagnosed patients -- because of the risks associated with the procedure.
Indeed, an Italian study summarized in a poster at Saturday's session showed that, in a sample of the allogeneic stem cell transplants carried out in Italy from 2000 to 2009, about 30 percent of the patients who received the treatment died as a result of the treatment itself. And that estimate is in line with previously published estimates of the so-called "treatment-related mortality" of allo transplants.
(Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37309.html )
Advances are being made, however, in the way allo transplants are being conducted, and the advances are reducing the risk of the treatment while also making it more effective.
Thus, researchers at Memorial Sloan-Kettering in New York City decided to test a sophisticated allo transplant approach as a treatment for myeloma patients who have not responded well to an auto (own stem cell) transplant, and most of whom also had indications of high-risk disease based on genetic testing.
The Sloan-Kettering study was small, involving only 13 patients. The allo transplant used during the study was a so-called "t-cell depleted" allo transplant, where the concentration of a specific kind of white blood cell (t-cells) is reduced in the donor's stem cells to reduce the risk associated with the procedure.
In addition, after patients received their transplant and began to show a response, they were eligible to receive "donor lymphocyte infusions", which are infusions of the stem donors white blood cells, designed to improve the efficacy of the allo transplant.
Of the original 13 patients in the Sloan-Kettering study, nine are still alive after a follow-up time of between 19 and 45 months post transplant. Estimated one-year survival based on the trial results is 69 percent, which is also the estimated two-year survival.
The researchers believe the results of this trial point to an effective way of dealing with disease relapse in patients with high risk genetic markers, and they have started a larger trial to further test the treatment approach.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper42075.html
For an extended discussion here in the forum about donor lymphocyte infusions for allo transplant patients, see this link:
https://myelomabeacon.org/forum/donor-lymphocyte-infusions-dli-for-multiple-myeloma-t744.html
As most Beacon readers know, allogeneic stem cell transplantation is a potentially curative therapy for myeloma. However, up until recently, it has not been carried out frequently on myeloma patients -- particularly newly diagnosed patients -- because of the risks associated with the procedure.
Indeed, an Italian study summarized in a poster at Saturday's session showed that, in a sample of the allogeneic stem cell transplants carried out in Italy from 2000 to 2009, about 30 percent of the patients who received the treatment died as a result of the treatment itself. And that estimate is in line with previously published estimates of the so-called "treatment-related mortality" of allo transplants.
(Abstract: http://ash.confex.com/ash/2011/webprogram/Paper37309.html )
Advances are being made, however, in the way allo transplants are being conducted, and the advances are reducing the risk of the treatment while also making it more effective.
Thus, researchers at Memorial Sloan-Kettering in New York City decided to test a sophisticated allo transplant approach as a treatment for myeloma patients who have not responded well to an auto (own stem cell) transplant, and most of whom also had indications of high-risk disease based on genetic testing.
The Sloan-Kettering study was small, involving only 13 patients. The allo transplant used during the study was a so-called "t-cell depleted" allo transplant, where the concentration of a specific kind of white blood cell (t-cells) is reduced in the donor's stem cells to reduce the risk associated with the procedure.
In addition, after patients received their transplant and began to show a response, they were eligible to receive "donor lymphocyte infusions", which are infusions of the stem donors white blood cells, designed to improve the efficacy of the allo transplant.
Of the original 13 patients in the Sloan-Kettering study, nine are still alive after a follow-up time of between 19 and 45 months post transplant. Estimated one-year survival based on the trial results is 69 percent, which is also the estimated two-year survival.
The researchers believe the results of this trial point to an effective way of dealing with disease relapse in patients with high risk genetic markers, and they have started a larger trial to further test the treatment approach.
Abstract:
http://ash.confex.com/ash/2011/webprogram/Paper42075.html
For an extended discussion here in the forum about donor lymphocyte infusions for allo transplant patients, see this link:
https://myelomabeacon.org/forum/donor-lymphocyte-infusions-dli-for-multiple-myeloma-t744.html
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