Higher Risk Multiple Myeloma
What is higher risk multiple myeloma? I have included Relapse, Refractory, and High Risk Disease in this category. One thing that myeloma specialists and researchers have found is that myeloma becomes resistant to treatment over time. In fact in some cases a disease that starts out as low risk may one day progress to high risk. That is why the treatments of these higher risk diseases is so important. Dr. Hari, who has some of the very best survival rates in the world, discussed disease progression and the treatment of relapse, refractory and high risk multiple myeloma on a recent Myeloma Cure Panel broadcast. You can hear this "CAN'T MISS" broadcast at: http://www.blogtalkradio.com/curepanel/2012/09/25/the-myeloma-cure-panel-talk-show
In the case of relapse, this is when your initial treatment is completed and your disease has progressed. It therefore requires additional treatment, and your original treatment plan may or may not work again to control the disease.
Refractory is the next step in the disease progression, and is when the disease has returned and the prior treatment has been tried again, but this time has failed. There may or may not be other drugs that work, but the prior drug will not work in the current configuration, and as a result is refractory to the disease. For example, if you have tried Revlimid and Velcade and you no longer respond to these drugs, you can now be treated with the new drug Carfilzomib. The dictionary definition of refractory is "resistant to treatment or cure".
High Risk multiple myeloma is the last step in the progression of risk in multiple myeloma. High Risk multiple myeloma represents about 15% of all myeloma cases, however it has historically had a life expectancy that is one half of that for Low Risk disease. The definition of high risk is represented differently by different myeloma specialists. The Mayo mSmart program defines high risk in the following link: http://msmart.org/newly%20diagnosed%20myeloma.pdf Risk is represented by both chromosome characteristics, and gene expression profiling. UAMS(University of Arkansas for Medical Sciences) uses gene expression profiling of 70 genes to determine the risk. However, what the patient is most concerned with is that this type of myeloma is far more difficult to treat, and as a result you need the input from someone who has treated and knows the challenges of high risk multiple myeloma. Bart Barlogie of UAMS and Dr. Fonseca of Mayo Clinic (Scottsdale), both expert in high risk disease provided an excellent description of their views on high risk myeloma, and you can find this at the following link: http://www.cancereducation.com/cancersyspagesnb/a/mmrf/mm0608e/MM06-08cFullTranscript.pdf
This section of www.myelomasurvival.com has been the most difficult to write. But I believe it is because this is the most difficult and challenging aspect about this disease. This is where the real complexity of the disease is highlighted, and it is in this phase of the disease that the skill of the multiple myeloma specialist becomes more valuable and necessary for your improved survival and life expectancy. As each patient goes through these levels of disease progression, the myeloma specialists expertise and knowledge and yes, access to clinical trials and developmental drugs becomes more and more critical to your prognosis. The following is set up in the three categories that I discussed above and will include the best clinical trials and treatments I can find for each of the them.
Relapse
This happens to be one of the aspects of the disease that all patients fear and dread. Your doctor has provided a treatment plan, and it has worked, you are thankful to have a CR(complete response), PR(partial response), or several other outcomes, but at least your disease is not progressing. You may be taken off drugs, and you now wait for the other foot to fall with fear and dread. RELAPSE! It is at this phase that you MUST have a myeloma specialist on your team. What are the three most important things required when your disease has relapsed or is refractory? SPECIALIST! SPECIALIST! SPECIALIST!!
You have had your specialist on board for a while, and he is knowledgeable of your treatment plan, knows how long it has been effective(how durable it is), what negative prognostic indicators are present, and determines whether you should continue your prior treatment, or modify it because of growing resistance to your current treatment. Some people have a great response to a specific drug and it may work again and again at relapse.
What I will do now is to give you a little bedtime reading. The following are articles by myeloma specialists who will totally confuse you and make your heads spin. They do not mean to, but like a nuclear physicist, they speak in a language that is not necessarily patient friendly, but it also speaks to the level of skill and training required to understand this disease. The first is from Dr. Anderson of Dana Farber, a thought leader in the myeloma field at link: http://myeloma.org/pdfs/EmergingtherapiesEJHDimopoulos.pdf The second is from the new head of the myeloma program at the University of Chicago, Dr. Andrzej Jakubowiak at the link: http://download.journals.elsevierhealth.com/pdfs/journals/0037-1963/PIIS0037196312000376.pdf There are many more that I could share, however I know that this probably put most of you to sleep, had your heads spinning, or just bored you to tears, but this same information is what gets the myeloma specialist up in the morning and makes them tick. Don't you want someone like that on your team?
At relapse the plan will be determined by the your specialist. This plan will be dependent on the myeloma specialists treatment philosophy, the risk profile of your disease, prior treatments, and the success of those treatments. I will place the treatment philosophies into three different groups, all of which have advantages and all that have shown excellent results. I will call them 1) Quality of Life approach 2) Aggressive approach and 3) The Balanced approach.
1) Quality of Life approach - This may also be the minimalist approach, or the use of the least amount of drugs to obtain control of the disease. You will go through the available drugs in sequence, depending on the risk factors and prior treatments. If Rd, revlimid and dex, was successful and durable you will continue with the same treatment at relapse, and if not durable go to the next drug, which could be Velcade and dex. Dr Berenson and Dr. Durie are two specialists that follow this strategy.
2) The Aggressive approach - This approach is one that is championed by Bart Barlogie of UAMS. His strategy is to hit the disease with all available drugs at initial treatment when the disease has not had any chance at developing a resistance to any of the drugs. This includes VRD-PACE, dual stem cell transplants, consolidation therapy and three years of VRd maintenance. The objective and his results have shown he can achieve a 60% cure rate in all of his low risk patients. At relapse the general procedure is to conduct another stem cell transplant. Dr. Tricot also is a proponent of this philosophy. For full disclosure this is the program that I chose to follow with very good results.
3) The Balanced approach - This I think is by far the most common approach and is the one that is probably best exemplified by Mayo clinics mSmart program. Based on your risk factor, you will be given the initial therapy as outlined in the link: http://msmart.org/newly%20diagnosed%20myeloma.pdf , and at relapse the specialists follow the procedure as outlined at the following link: http://msmart.org/Relapsed%20Myeloma.pdf . Dr. Hari, who has some of the best survival rates, follows a process similar to this.
All of the treatments outlined on the www.myelomasurvival.com home page can be applied in the case of relapse, however it should be left to your own research and the skill of your myeloma specialist, in determining exactly which treatment plan to pursue. In the end you are in control, and it is YOUR plan!
Refractory Multiple Myeloma
Did I mention the three most important things you need when your disease is relapsed or refractory? Well it is even more important when your disease has progressed to the point where it is thumbing its nose at prior treatments. It is my hope that your never get to this point, or that if it does happen, it is far into the future when there are far more promising approaches to the refractory disease. The good news is that in the last several years we have had the newer, novel drugs of Thalidomide, Velcade, Revlimid, and now Carfilzomib and Pomalyst, that show positive results either with dexamethasone(dex), or in combination with each other and dex(dexamethasone). So if you have been on a regiment that includes Revlimid like Rd, you may have a great response with any of the combinations that include Velcade or Carfilzomib.
In addition, if you have a myeloma specialist on your team that is involved with Clinical Trials or the use of drugs not approved by the FDA but may be available for "compassionate use", then those options are also available as well. Ok, so let's just see what kind of recent treatment and clinical trials that show promising results for the refractory patients are currently available. Another good bit of bedtime reading includes the following by Dr. Lionel of Emory University and Dr. Richardson of Dana Farber. Link: http://clincancerres.aacrjournals.org/content/17/6/1264.full They provide information on many studies, some of the more interesting which include :
VRD(Velcade, Revlimid, Dexemethasone) - 69% ORR(Overall Response Rate) - 29 month OS(Overall Survival)
RCD(Revlimid, Cyclophosphamide, Dex) - 81% ORR
V/PLB(Vecade, Peglylated Liposomal Doxorubicin) - 63% ORR - 38.3 months OS
T/PLB/D(Thalidimide,PL Doxorubincin, Dex) - 76% ORR - >22 months OS because PFS(progression free survival) is 22 months
More recent studies include the following treatments and outcomes for relapsed and refractory patients.
KPD(Kyprolis, Pomalyst, Dexamethasone) - 70% ORR - median OS(Overall Survival) had not been reached at 18 months
KRd(carfilzomib, lenalidomide, and low-dose dexamethasone) - 69% ORR - PFS of 15.4 months
ERd(Elotuzumab, lenalidomide, and Dexamethasone) - 79% ORR - PFS of 19.4 months
DaraRD(Daratumumab, lenalidomide, and Dexamthasone) - 88% ORR - PFS not reached at 12 months
The most recent addition to available approved treatments is for single agent Carfilzomib and Pomalidemide, which has been recently approved for relapsed myeloma. Link: http://bloodjournal.hematologylibrary.org/content/early/2012/07/24/blood-2012-05-425934.abstract The study results for Carfilzomib were - 23% ORR -15.6 months OS. These results will surely show improvement with combination therapy like CzRd(Carfilzomib, Revlimid, and dex), which showed such great results in the newly diagnosed patients and a 78% response rate in a clinical trial for relapsed and refractory patients. Link: http://www.clinicaloncology.com/ViewArticle.aspx?d=Hematologic%2BMalignancies&d_id=149&i=September+2012&i_id=887&a_id=21716 A summary of the Pomalidemide FDA approval can be found at the link: http://www.medscape.com/viewarticle/779048 There are a number of Clinical Trials, that include Elotuzumab, Daratumumab, SAR65098, Panabinastat, and many other drugs that have shown promise in the refractory setting, however the availability of these for any patient's care depends on which myeloma specialists are involved in these studies. The most skilled and knowledgeable specialists will be far more versed in how to get his patients into these trials. I hope that each of you have a skilled myeloma professional on your team to provide the proper guidance, and a second opinion for verification.
High Risk Multiple Myeloma
Until recently high risk disease has been the most difficult area of multiple myeloma. High risk multiple myeloma, whether defined by the FISH test or gene expression profiling is by far the most difficult to treat. The good news is that most people with myeloma are in the low risk category(85%), and those at high risk are only 15%. Historically, high risk disease will respond to therapy, but it is usually not a durable response. As stated previously, UAMS(University of Arkansas for Medical Sciences) and Mayo (Scottsdale) have been in the thought leadership position for high risk disease. They have provided risk adapted therapy for this disease, but have not been able to duplicate the success achieved in the treatment of the low risk disease. The Mayo mSmart program for all of the Mayo hospitals suggests induction therapy(initial) with VRD(Velcade, Revlimid, and dex), followed by a stem cell transplant. UAMS has two clinical trials for high risk patients, Total Therapy 5(TT5) and TT6. All of the treatments that are outlined on the home page can be used for the high risk patient, but they again will not be nearly as durable as they will be for the low risk patient.
I think Dr. Craig Hofmeister from The James Cancer Hospital at Ohio State University provided a frank and realistic evaluation of the current state of treatment for the high risk patient. He stated, " I think the overall feeling is that for patients that are truly high risk (high beta2 microglobulin + high risk genetics such as 17p deletion or t(14;16)), all treatments are going to work only transiently and maintenance of response will quickly become impossible. The development of highly effective new therapies is critical for these patients with very proliferative disease." Again, the need for access to the best new clinical trials must be part of the high risk patients treatment strategy. And Dr. Hofmeister's belief that a high risk solution will come from clinical trials has recently borne some fruit. Dr. Sagar Lonial, with the Winship Cancer Institute at Emory University in Atlanta has reported a sturdy on newly diagnosed myeloma patient with high risk disease that has show remarkable results. A recent publication in Leukemia states.
"We evaluated a combination maintenance/consolidation regimen (RVD) following autologous stem cell transplant (ASCT) for high-risk patients to evaluate the impact of this approach on outcome. Following initiation of RVD maintenance, 51% of patients achieved stringent complete response (sCR), with 96% achieving at least VGPR as best response. Median progression free survival (PFS) for all patients is 32 months with a 3-year OS of 93%. The regimen was well tolerated with no grade 3/4 neuropathy. Early ASCT followed by RVD maintenance is a promising strategy for high-risk myeloma patients and delivered excellent response rates, and promising PFS and OS."
The National Cancer Institutes lists the average 3 year relative survival of all patients(high and low risk) at 60%, and the 3 year relative survival for the Emory trial is 98.8%. This is a truly remarkable performance, where the subjects in the trial have a 3 year life expectancy nearly equal to the general population at age 70.
I hope that you find this information valuable in your search to find the best possible multiple myeloma treatment plan. And may God Bless your myeloma journey!
In the case of relapse, this is when your initial treatment is completed and your disease has progressed. It therefore requires additional treatment, and your original treatment plan may or may not work again to control the disease.
Refractory is the next step in the disease progression, and is when the disease has returned and the prior treatment has been tried again, but this time has failed. There may or may not be other drugs that work, but the prior drug will not work in the current configuration, and as a result is refractory to the disease. For example, if you have tried Revlimid and Velcade and you no longer respond to these drugs, you can now be treated with the new drug Carfilzomib. The dictionary definition of refractory is "resistant to treatment or cure".
High Risk multiple myeloma is the last step in the progression of risk in multiple myeloma. High Risk multiple myeloma represents about 15% of all myeloma cases, however it has historically had a life expectancy that is one half of that for Low Risk disease. The definition of high risk is represented differently by different myeloma specialists. The Mayo mSmart program defines high risk in the following link: http://msmart.org/newly%20diagnosed%20myeloma.pdf Risk is represented by both chromosome characteristics, and gene expression profiling. UAMS(University of Arkansas for Medical Sciences) uses gene expression profiling of 70 genes to determine the risk. However, what the patient is most concerned with is that this type of myeloma is far more difficult to treat, and as a result you need the input from someone who has treated and knows the challenges of high risk multiple myeloma. Bart Barlogie of UAMS and Dr. Fonseca of Mayo Clinic (Scottsdale), both expert in high risk disease provided an excellent description of their views on high risk myeloma, and you can find this at the following link: http://www.cancereducation.com/cancersyspagesnb/a/mmrf/mm0608e/MM06-08cFullTranscript.pdf
This section of www.myelomasurvival.com has been the most difficult to write. But I believe it is because this is the most difficult and challenging aspect about this disease. This is where the real complexity of the disease is highlighted, and it is in this phase of the disease that the skill of the multiple myeloma specialist becomes more valuable and necessary for your improved survival and life expectancy. As each patient goes through these levels of disease progression, the myeloma specialists expertise and knowledge and yes, access to clinical trials and developmental drugs becomes more and more critical to your prognosis. The following is set up in the three categories that I discussed above and will include the best clinical trials and treatments I can find for each of the them.
Relapse
This happens to be one of the aspects of the disease that all patients fear and dread. Your doctor has provided a treatment plan, and it has worked, you are thankful to have a CR(complete response), PR(partial response), or several other outcomes, but at least your disease is not progressing. You may be taken off drugs, and you now wait for the other foot to fall with fear and dread. RELAPSE! It is at this phase that you MUST have a myeloma specialist on your team. What are the three most important things required when your disease has relapsed or is refractory? SPECIALIST! SPECIALIST! SPECIALIST!!
You have had your specialist on board for a while, and he is knowledgeable of your treatment plan, knows how long it has been effective(how durable it is), what negative prognostic indicators are present, and determines whether you should continue your prior treatment, or modify it because of growing resistance to your current treatment. Some people have a great response to a specific drug and it may work again and again at relapse.
What I will do now is to give you a little bedtime reading. The following are articles by myeloma specialists who will totally confuse you and make your heads spin. They do not mean to, but like a nuclear physicist, they speak in a language that is not necessarily patient friendly, but it also speaks to the level of skill and training required to understand this disease. The first is from Dr. Anderson of Dana Farber, a thought leader in the myeloma field at link: http://myeloma.org/pdfs/EmergingtherapiesEJHDimopoulos.pdf The second is from the new head of the myeloma program at the University of Chicago, Dr. Andrzej Jakubowiak at the link: http://download.journals.elsevierhealth.com/pdfs/journals/0037-1963/PIIS0037196312000376.pdf There are many more that I could share, however I know that this probably put most of you to sleep, had your heads spinning, or just bored you to tears, but this same information is what gets the myeloma specialist up in the morning and makes them tick. Don't you want someone like that on your team?
At relapse the plan will be determined by the your specialist. This plan will be dependent on the myeloma specialists treatment philosophy, the risk profile of your disease, prior treatments, and the success of those treatments. I will place the treatment philosophies into three different groups, all of which have advantages and all that have shown excellent results. I will call them 1) Quality of Life approach 2) Aggressive approach and 3) The Balanced approach.
1) Quality of Life approach - This may also be the minimalist approach, or the use of the least amount of drugs to obtain control of the disease. You will go through the available drugs in sequence, depending on the risk factors and prior treatments. If Rd, revlimid and dex, was successful and durable you will continue with the same treatment at relapse, and if not durable go to the next drug, which could be Velcade and dex. Dr Berenson and Dr. Durie are two specialists that follow this strategy.
2) The Aggressive approach - This approach is one that is championed by Bart Barlogie of UAMS. His strategy is to hit the disease with all available drugs at initial treatment when the disease has not had any chance at developing a resistance to any of the drugs. This includes VRD-PACE, dual stem cell transplants, consolidation therapy and three years of VRd maintenance. The objective and his results have shown he can achieve a 60% cure rate in all of his low risk patients. At relapse the general procedure is to conduct another stem cell transplant. Dr. Tricot also is a proponent of this philosophy. For full disclosure this is the program that I chose to follow with very good results.
3) The Balanced approach - This I think is by far the most common approach and is the one that is probably best exemplified by Mayo clinics mSmart program. Based on your risk factor, you will be given the initial therapy as outlined in the link: http://msmart.org/newly%20diagnosed%20myeloma.pdf , and at relapse the specialists follow the procedure as outlined at the following link: http://msmart.org/Relapsed%20Myeloma.pdf . Dr. Hari, who has some of the best survival rates, follows a process similar to this.
All of the treatments outlined on the www.myelomasurvival.com home page can be applied in the case of relapse, however it should be left to your own research and the skill of your myeloma specialist, in determining exactly which treatment plan to pursue. In the end you are in control, and it is YOUR plan!
Refractory Multiple Myeloma
Did I mention the three most important things you need when your disease is relapsed or refractory? Well it is even more important when your disease has progressed to the point where it is thumbing its nose at prior treatments. It is my hope that your never get to this point, or that if it does happen, it is far into the future when there are far more promising approaches to the refractory disease. The good news is that in the last several years we have had the newer, novel drugs of Thalidomide, Velcade, Revlimid, and now Carfilzomib and Pomalyst, that show positive results either with dexamethasone(dex), or in combination with each other and dex(dexamethasone). So if you have been on a regiment that includes Revlimid like Rd, you may have a great response with any of the combinations that include Velcade or Carfilzomib.
In addition, if you have a myeloma specialist on your team that is involved with Clinical Trials or the use of drugs not approved by the FDA but may be available for "compassionate use", then those options are also available as well. Ok, so let's just see what kind of recent treatment and clinical trials that show promising results for the refractory patients are currently available. Another good bit of bedtime reading includes the following by Dr. Lionel of Emory University and Dr. Richardson of Dana Farber. Link: http://clincancerres.aacrjournals.org/content/17/6/1264.full They provide information on many studies, some of the more interesting which include :
VRD(Velcade, Revlimid, Dexemethasone) - 69% ORR(Overall Response Rate) - 29 month OS(Overall Survival)
RCD(Revlimid, Cyclophosphamide, Dex) - 81% ORR
V/PLB(Vecade, Peglylated Liposomal Doxorubicin) - 63% ORR - 38.3 months OS
T/PLB/D(Thalidimide,PL Doxorubincin, Dex) - 76% ORR - >22 months OS because PFS(progression free survival) is 22 months
More recent studies include the following treatments and outcomes for relapsed and refractory patients.
KPD(Kyprolis, Pomalyst, Dexamethasone) - 70% ORR - median OS(Overall Survival) had not been reached at 18 months
KRd(carfilzomib, lenalidomide, and low-dose dexamethasone) - 69% ORR - PFS of 15.4 months
ERd(Elotuzumab, lenalidomide, and Dexamethasone) - 79% ORR - PFS of 19.4 months
DaraRD(Daratumumab, lenalidomide, and Dexamthasone) - 88% ORR - PFS not reached at 12 months
The most recent addition to available approved treatments is for single agent Carfilzomib and Pomalidemide, which has been recently approved for relapsed myeloma. Link: http://bloodjournal.hematologylibrary.org/content/early/2012/07/24/blood-2012-05-425934.abstract The study results for Carfilzomib were - 23% ORR -15.6 months OS. These results will surely show improvement with combination therapy like CzRd(Carfilzomib, Revlimid, and dex), which showed such great results in the newly diagnosed patients and a 78% response rate in a clinical trial for relapsed and refractory patients. Link: http://www.clinicaloncology.com/ViewArticle.aspx?d=Hematologic%2BMalignancies&d_id=149&i=September+2012&i_id=887&a_id=21716 A summary of the Pomalidemide FDA approval can be found at the link: http://www.medscape.com/viewarticle/779048 There are a number of Clinical Trials, that include Elotuzumab, Daratumumab, SAR65098, Panabinastat, and many other drugs that have shown promise in the refractory setting, however the availability of these for any patient's care depends on which myeloma specialists are involved in these studies. The most skilled and knowledgeable specialists will be far more versed in how to get his patients into these trials. I hope that each of you have a skilled myeloma professional on your team to provide the proper guidance, and a second opinion for verification.
High Risk Multiple Myeloma
Until recently high risk disease has been the most difficult area of multiple myeloma. High risk multiple myeloma, whether defined by the FISH test or gene expression profiling is by far the most difficult to treat. The good news is that most people with myeloma are in the low risk category(85%), and those at high risk are only 15%. Historically, high risk disease will respond to therapy, but it is usually not a durable response. As stated previously, UAMS(University of Arkansas for Medical Sciences) and Mayo (Scottsdale) have been in the thought leadership position for high risk disease. They have provided risk adapted therapy for this disease, but have not been able to duplicate the success achieved in the treatment of the low risk disease. The Mayo mSmart program for all of the Mayo hospitals suggests induction therapy(initial) with VRD(Velcade, Revlimid, and dex), followed by a stem cell transplant. UAMS has two clinical trials for high risk patients, Total Therapy 5(TT5) and TT6. All of the treatments that are outlined on the home page can be used for the high risk patient, but they again will not be nearly as durable as they will be for the low risk patient.
I think Dr. Craig Hofmeister from The James Cancer Hospital at Ohio State University provided a frank and realistic evaluation of the current state of treatment for the high risk patient. He stated, " I think the overall feeling is that for patients that are truly high risk (high beta2 microglobulin + high risk genetics such as 17p deletion or t(14;16)), all treatments are going to work only transiently and maintenance of response will quickly become impossible. The development of highly effective new therapies is critical for these patients with very proliferative disease." Again, the need for access to the best new clinical trials must be part of the high risk patients treatment strategy. And Dr. Hofmeister's belief that a high risk solution will come from clinical trials has recently borne some fruit. Dr. Sagar Lonial, with the Winship Cancer Institute at Emory University in Atlanta has reported a sturdy on newly diagnosed myeloma patient with high risk disease that has show remarkable results. A recent publication in Leukemia states.
"We evaluated a combination maintenance/consolidation regimen (RVD) following autologous stem cell transplant (ASCT) for high-risk patients to evaluate the impact of this approach on outcome. Following initiation of RVD maintenance, 51% of patients achieved stringent complete response (sCR), with 96% achieving at least VGPR as best response. Median progression free survival (PFS) for all patients is 32 months with a 3-year OS of 93%. The regimen was well tolerated with no grade 3/4 neuropathy. Early ASCT followed by RVD maintenance is a promising strategy for high-risk myeloma patients and delivered excellent response rates, and promising PFS and OS."
The National Cancer Institutes lists the average 3 year relative survival of all patients(high and low risk) at 60%, and the 3 year relative survival for the Emory trial is 98.8%. This is a truly remarkable performance, where the subjects in the trial have a 3 year life expectancy nearly equal to the general population at age 70.
I hope that you find this information valuable in your search to find the best possible multiple myeloma treatment plan. And may God Bless your myeloma journey!