"The idea that the same molecular drivers are present in very different and sometimes apparently unrelated cancers is driving new areas of inquiry in drug development and shaking up the way oncologists think about treating their patients. That research will be on display and under debate at the American Society of Clinical Oncology annual meeting in Chicago June 1-5.
“We now understand that it’s not sufficient to identify a tumor based on the histology or the organ of origin, as we did traditionally, but rather … tumors are heterogeneous, and we need to understand the particular molecular driver of the tumor to select appropriate therapy,” ASCO President Michael Link said during a May 16 press conference to highlight research being presented at this year’s meeting."
more here:
http://www.oncologystat.com/news/Precision_Medicine_Will_Be_in_Action_at_ASCO.html
Forums
Re: Precision Medicine will be in Action @ ASCO 2012
Tweet aggregates at ASCO 2012 that may provide updates to look for and sessions running:
http://pharmastrategyblog.com/2012/06/aggregating-the-2012-asco-tweets.html/
http://pharmastrategyblog.com/2012/06/aggregating-the-2012-asco-tweets.html/
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Precision Medicine will be in Action @ ASCO 2012
I recognize that the Precision Medicine article is not specific to multiple myeloma however it bodes well for how cancer treatment will progress.
We already know that the ISS staging process does not necessarily reflect the pathogeniticy of the disease..i.e aggressiveness and malignancy.
I suspect this is why PR outcomes can have greater PFS than those with CR's IR's or MR's ..and go on to have very short PFS and survival outcomes, despite the CR's going submitting to HDT.
This I suspect also may explain why Depth of Response, is not necessarily indicate of sustained CR's with HDT. The question becomes why would someone with Minimal Residue Disease (MRD) prior to HDT and having an MR go on to rapid progression following HDT and someone with a PR not? After all the HDT obliterates the immune system so how much more could be done, and it accounts for why there is no difference in outcomes between delayed and immediate HDT.
All multiple myeloma is not equal.based on staging and knowing the specific pathogeneticity of your individual multiple myeloma can make a difference.
We see this already with Breast cancer...patients with estrogen receptive breast cancer have a far better prognosis than someone with inflammatory Breast Cancer, despite the stage at diagnosis.
What role is inflammation playing? Several articles talk about the imbalance of Th1/Th2 in the immune system. And that part of the response of the immune system is inflammation when it sets out to kill foreign bodies .. so to what degree can we suppress the immune system and keep it from the inflammatory process that results in normal humeral cytotoxicity?
This inflammatory process has also been identified as one of the reasons that anti-inflammatory agents such as COX inhibitors have been shown to be anti cancercinogic along with steroids.
Many questions...
I personally feel we are on the cusp of not just innovative therapies, that preclude lethal doses of chemotherapy but revolutionize how we treat multiple myeloma. We are seeing some of this presently with the new protesome and HDAC inhibitors along with the MEK inhibitors (discussed in article) as well as Akt inhibitors and T-cell altered lymphocytes.
Would love to hear/discuss what others are thinking along these lines.
We already know that the ISS staging process does not necessarily reflect the pathogeniticy of the disease..i.e aggressiveness and malignancy.
I suspect this is why PR outcomes can have greater PFS than those with CR's IR's or MR's ..and go on to have very short PFS and survival outcomes, despite the CR's going submitting to HDT.
This I suspect also may explain why Depth of Response, is not necessarily indicate of sustained CR's with HDT. The question becomes why would someone with Minimal Residue Disease (MRD) prior to HDT and having an MR go on to rapid progression following HDT and someone with a PR not? After all the HDT obliterates the immune system so how much more could be done, and it accounts for why there is no difference in outcomes between delayed and immediate HDT.
All multiple myeloma is not equal.based on staging and knowing the specific pathogeneticity of your individual multiple myeloma can make a difference.
We see this already with Breast cancer...patients with estrogen receptive breast cancer have a far better prognosis than someone with inflammatory Breast Cancer, despite the stage at diagnosis.
What role is inflammation playing? Several articles talk about the imbalance of Th1/Th2 in the immune system. And that part of the response of the immune system is inflammation when it sets out to kill foreign bodies .. so to what degree can we suppress the immune system and keep it from the inflammatory process that results in normal humeral cytotoxicity?
This inflammatory process has also been identified as one of the reasons that anti-inflammatory agents such as COX inhibitors have been shown to be anti cancercinogic along with steroids.
Many questions...
I personally feel we are on the cusp of not just innovative therapies, that preclude lethal doses of chemotherapy but revolutionize how we treat multiple myeloma. We are seeing some of this presently with the new protesome and HDAC inhibitors along with the MEK inhibitors (discussed in article) as well as Akt inhibitors and T-cell altered lymphocytes.
Would love to hear/discuss what others are thinking along these lines.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Precision Medicine will be in Action @ ASCO 2012
Suzierose,
What study has ever shown a high percentage of Myeloma patients losing a Molecular Response quickly and not having good outcomes? Here are the 3 most recent Molecular Response studies on Myeloma patients I am aware of. Using HDT to 4 cycles of VTD and no maintenance - the first patient that gained MR lost remission more than 4 years later - you consider that losing remission quickly?
https://ash.confex.com/ash/2011/webprogram/Paper36584.html
In this one patients did HDT to HDT Partially T Cell depleted Allo. No maintenance therapy is used. This is what the study author concluded for patients that held 3 consecutive MRs:
'Those patients, who achieved molecular remission, have a high probability of long-term disease-freedom and of cure."
"The study underlines the importance of the depth of remission and shows that achieving molecular remission as determined by myeloma-specific IgH gene rearrangements and plasma cell chimerism is associated with long-term freedom from disease and potential cure of multiple myeloma in an auto-/allo SCT approach.'
https://ash.confex.com/ash/2011/webprogram/Paper42900.html
Those survival curves do not look like a lot of patients are losing MR quickly. I have never seen survival curves like that with patients with a Partial Response. In the first study OS is 100% at 5 years and in the second it is 91% for patients that got at least one MR.
Dr. Kroger also did a study on patients that failed to get a CR after Allo transplant. He upgraded responses using DLI's and Novel agents. Here are the statistics from that trial:
"Achievement of CR resulted in improved 5-year progressive-free and overall survival, according to European Group for Blood and Marrow Transplantation criteria (53% vs 35%; p=0.03 and 90% vs 62%; p=0.06), flow cytometry (74% vs 15%; p=0.001 and 100% vs 52%; p=0.1), or molecular methods (84% vs 38%; p=0.001 and 100% vs 71%; p=0.03)."
http://www.exphem.org/article/S0301-472X(09)00116-7/abstract
Is there a recent study on MR that I am not aware of? Could you point to any study that suggests patients that get MR " and go on to have very short PFS and survival outcomes, despite the CR's going submitting to HDT."
I would also add these patients are not on never ending cycles of myeloma therapy like the "Big Pharma Shills" treating multiple myeloma usually treat their patients. The depth of response not mattering argument only holds up to stringent complete response. Every patient in the above 3 studies had HDT.
Mark
What study has ever shown a high percentage of Myeloma patients losing a Molecular Response quickly and not having good outcomes? Here are the 3 most recent Molecular Response studies on Myeloma patients I am aware of. Using HDT to 4 cycles of VTD and no maintenance - the first patient that gained MR lost remission more than 4 years later - you consider that losing remission quickly?
https://ash.confex.com/ash/2011/webprogram/Paper36584.html
In this one patients did HDT to HDT Partially T Cell depleted Allo. No maintenance therapy is used. This is what the study author concluded for patients that held 3 consecutive MRs:
'Those patients, who achieved molecular remission, have a high probability of long-term disease-freedom and of cure."
"The study underlines the importance of the depth of remission and shows that achieving molecular remission as determined by myeloma-specific IgH gene rearrangements and plasma cell chimerism is associated with long-term freedom from disease and potential cure of multiple myeloma in an auto-/allo SCT approach.'
https://ash.confex.com/ash/2011/webprogram/Paper42900.html
Those survival curves do not look like a lot of patients are losing MR quickly. I have never seen survival curves like that with patients with a Partial Response. In the first study OS is 100% at 5 years and in the second it is 91% for patients that got at least one MR.
Dr. Kroger also did a study on patients that failed to get a CR after Allo transplant. He upgraded responses using DLI's and Novel agents. Here are the statistics from that trial:
"Achievement of CR resulted in improved 5-year progressive-free and overall survival, according to European Group for Blood and Marrow Transplantation criteria (53% vs 35%; p=0.03 and 90% vs 62%; p=0.06), flow cytometry (74% vs 15%; p=0.001 and 100% vs 52%; p=0.1), or molecular methods (84% vs 38%; p=0.001 and 100% vs 71%; p=0.03)."
http://www.exphem.org/article/S0301-472X(09)00116-7/abstract
Is there a recent study on MR that I am not aware of? Could you point to any study that suggests patients that get MR " and go on to have very short PFS and survival outcomes, despite the CR's going submitting to HDT."
I would also add these patients are not on never ending cycles of myeloma therapy like the "Big Pharma Shills" treating multiple myeloma usually treat their patients. The depth of response not mattering argument only holds up to stringent complete response. Every patient in the above 3 studies had HDT.
Mark
-
Mark
Re: Precision Medicine will be in Action @ ASCO 2012
Hi Mark!!
You ask:
What study has ever shown a high percentage of Myeloma patients losing a Molecular Response quickly and not having good outcomes? Here are the 3 most recent Molecular Response studies on Myeloma patients I am aware of. Using HDT to 4 cycles of VTD and no maintenance - the first patient that gained MR lost remission more than 4 years later - you consider that losing remission quickly?
https://ash.confex.com/ash/2011/webprogram/Paper36584.html
I agree with you. Can't say that I know of folks losing MR quickly. But then, why would a patient with MR submit to HDT followed with SCT...after all how could they have a deeper response?
Typically, what the trial outcome/results show is that the patients with specific 'high risk variables' have far shorter PFS and dismal survival outcomes. To be honest, I have to say I can't recall data, broken down as you pose here. The writeups seem to focus on those who do have relapsed and do not have CR going on to HDT and how many of those achieve CR following HDT with SCT rescue.
http://www.ncbi.nlm.nih.gov/pubmed/22128143
"Our patients with t(4;14)(p16.3;q32) had a median time to progression of only 8.2 months after stem cell therapy and an overall survival of 18.8 months. This suggests that high-dose therapy, as currently practiced, has minimal benefit for these patients. Whether the addition of nonmyeloablative strategies will overcome these therapeutic limitations is not known; thus, the strategies cannot be deemed the best therapy for this high-risk group of patients. Also, the dismal outcome for t(4;14)(p16.3;q32) after a stem cell transplantation raises the question of the role of allogeneic transplantation in suitable younger candidates."
http://bloodjournal.hematologylibrary.org/content/106/8/2837.full
The point I have made is that HDT does not result in PFS of any length for those in the 'high risk' stratification. This has to be put in the context of what was feasible prior to IMID's/protesomes when the high risk patient may not have even achieved a CR, let alone an MR, and thus went for the HDT in hopes of doing so. However, they have now shown that this cohort of patients WILL NOT have a good outcome with HDT.
Those patients who fail to achieve CR and do NOT have the high risk variables were shown to have longer/sustained PFS.
Hope that point of clarification helps.
You ask:
What study has ever shown a high percentage of Myeloma patients losing a Molecular Response quickly and not having good outcomes? Here are the 3 most recent Molecular Response studies on Myeloma patients I am aware of. Using HDT to 4 cycles of VTD and no maintenance - the first patient that gained MR lost remission more than 4 years later - you consider that losing remission quickly?
https://ash.confex.com/ash/2011/webprogram/Paper36584.html
I agree with you. Can't say that I know of folks losing MR quickly. But then, why would a patient with MR submit to HDT followed with SCT...after all how could they have a deeper response?
Typically, what the trial outcome/results show is that the patients with specific 'high risk variables' have far shorter PFS and dismal survival outcomes. To be honest, I have to say I can't recall data, broken down as you pose here. The writeups seem to focus on those who do have relapsed and do not have CR going on to HDT and how many of those achieve CR following HDT with SCT rescue.
http://www.ncbi.nlm.nih.gov/pubmed/22128143
"Our patients with t(4;14)(p16.3;q32) had a median time to progression of only 8.2 months after stem cell therapy and an overall survival of 18.8 months. This suggests that high-dose therapy, as currently practiced, has minimal benefit for these patients. Whether the addition of nonmyeloablative strategies will overcome these therapeutic limitations is not known; thus, the strategies cannot be deemed the best therapy for this high-risk group of patients. Also, the dismal outcome for t(4;14)(p16.3;q32) after a stem cell transplantation raises the question of the role of allogeneic transplantation in suitable younger candidates."
http://bloodjournal.hematologylibrary.org/content/106/8/2837.full
The point I have made is that HDT does not result in PFS of any length for those in the 'high risk' stratification. This has to be put in the context of what was feasible prior to IMID's/protesomes when the high risk patient may not have even achieved a CR, let alone an MR, and thus went for the HDT in hopes of doing so. However, they have now shown that this cohort of patients WILL NOT have a good outcome with HDT.
Those patients who fail to achieve CR and do NOT have the high risk variables were shown to have longer/sustained PFS.
Hope that point of clarification helps.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Precision Medicine will be in Action @ ASCO 2012
Suzierose,
I am in a great mood tonight - my one year post Allo tests show my MR held - could I dare dream I will become one of "those patients" Dr. Kroger mentions in the study above?
My thought on treating Myeloma patients is right in line with Dr. Krogers. Here is the Beacon's report of what he said at 2011 ASH:
"And here is the key result:
Patients who achieved a sustained molecular remission had a 5 year overall survival of 91 percent, while those with mixed molecular remission resulted in a 5 year overall survival of 87 percent.
In other words, achieving molecular remission, whether sustained or mixed, has a significant impact on overall survival.
And this is one of the two key takeaways Dr. Kroeger said that he wanted people to take away from the presentation.
He said that it isn't important how or when a patient achieves molecular remission. If a patient is able to achieve molecular remission after their induction therapy, he doubts there's anything to be gained by doing anything further with the patient at that time.
If molecular remission is achieved after induction plus conditioning and an auto transplant, then an allo transplant isn't necessary in Dr. Kroeger's eyes.
But the key is to get patients to a molecular remission if at all possible.'
https://myelomabeacon.org/forum/post3262.html#p3262
This also suggests that maintenance is not necessary for a patient with MR.
I do not think Auto should be viewed as Consolidation. Alkylators (high dose or low) are good for debulking, not consolidating IMO. Note this from a discussion from 2010 about the Italian I referenced earlier (and all the time it seems!!!)
"To the best of our knowledge, this is the first study reporting a non-negligible rate of persistent MRs outside the context of allo-SCT programs. Several reports investigated this issue before the introduction of novel nonchemotherapeutic agents. Corradini et al9,10 reported the nearly constant persistence of PCR-detectable disease after auto-SCT. Our results are consistent with this experience since only one patient was PCR negative at study entry. Martinelli et al7 showed a slightly higher proportion of PCR negativity after auto-SCT."
'To put our results into perspective, it should be emphasized that only 20% of a highly selected population achieved MR. Nevertheless, only 15% of these patients were immunofixation-negative CR before consolidation, indicating the persistence of residual tumor burden that was effectively targeted by VTD. However, VTD does not have an ongoing antitumor effect such as graft-versus-myeloma,43 suggesting the possible future occurrence of molecular and clinical relapses, particularly considering that the median follow-up is presently 27 months. However, our nested PCR and RQ-PCR results showed that a post-transplant consolidation based on new drugs has a major antitumor activity on multiple myeloma cells surviving auto-SCT. VTD is unlikely to be the optimum choice to induce maximum cytoreduction after auto-SCT, and we foresee the possibility of developing more effective combinations, for example, by including lenalidomide.'
http://jco.ascopubs.org/content/28/12/2077.long
The problem with alkylators to IMIDs is that "minor secondary cancer thing". If you listen to this video by Dr. Anderson from Dana-Farber, at 5:35 he says the novel agents can kill myeloma cells bound to the bone marrow, but high dose alkylators cannot. So I agree 100% with the point that Auto is unnecessary for a patient that gets MR from Induction.
http://myeloma.org/ArticlePage.action?tabId=22&menuId=163&articleId=3295&aTab=-4&gParentType=link&gParentId=5510&parentIndexPageId=317
My only disagreement with you was that you put MR and IR in with sCR and CR and said patients with VGPR could have as good of an outcome as a patient with MR. There is a big improvement in outcomes when a patient gets MR or IR. IMO MR or IR should be the initial therapy goal for all patients.
Mark
I am in a great mood tonight - my one year post Allo tests show my MR held - could I dare dream I will become one of "those patients" Dr. Kroger mentions in the study above?
My thought on treating Myeloma patients is right in line with Dr. Krogers. Here is the Beacon's report of what he said at 2011 ASH:
"And here is the key result:
Patients who achieved a sustained molecular remission had a 5 year overall survival of 91 percent, while those with mixed molecular remission resulted in a 5 year overall survival of 87 percent.
In other words, achieving molecular remission, whether sustained or mixed, has a significant impact on overall survival.
And this is one of the two key takeaways Dr. Kroeger said that he wanted people to take away from the presentation.
He said that it isn't important how or when a patient achieves molecular remission. If a patient is able to achieve molecular remission after their induction therapy, he doubts there's anything to be gained by doing anything further with the patient at that time.
If molecular remission is achieved after induction plus conditioning and an auto transplant, then an allo transplant isn't necessary in Dr. Kroeger's eyes.
But the key is to get patients to a molecular remission if at all possible.'
https://myelomabeacon.org/forum/post3262.html#p3262
This also suggests that maintenance is not necessary for a patient with MR.
I do not think Auto should be viewed as Consolidation. Alkylators (high dose or low) are good for debulking, not consolidating IMO. Note this from a discussion from 2010 about the Italian I referenced earlier (and all the time it seems!!!)
"To the best of our knowledge, this is the first study reporting a non-negligible rate of persistent MRs outside the context of allo-SCT programs. Several reports investigated this issue before the introduction of novel nonchemotherapeutic agents. Corradini et al9,10 reported the nearly constant persistence of PCR-detectable disease after auto-SCT. Our results are consistent with this experience since only one patient was PCR negative at study entry. Martinelli et al7 showed a slightly higher proportion of PCR negativity after auto-SCT."
'To put our results into perspective, it should be emphasized that only 20% of a highly selected population achieved MR. Nevertheless, only 15% of these patients were immunofixation-negative CR before consolidation, indicating the persistence of residual tumor burden that was effectively targeted by VTD. However, VTD does not have an ongoing antitumor effect such as graft-versus-myeloma,43 suggesting the possible future occurrence of molecular and clinical relapses, particularly considering that the median follow-up is presently 27 months. However, our nested PCR and RQ-PCR results showed that a post-transplant consolidation based on new drugs has a major antitumor activity on multiple myeloma cells surviving auto-SCT. VTD is unlikely to be the optimum choice to induce maximum cytoreduction after auto-SCT, and we foresee the possibility of developing more effective combinations, for example, by including lenalidomide.'
http://jco.ascopubs.org/content/28/12/2077.long
The problem with alkylators to IMIDs is that "minor secondary cancer thing". If you listen to this video by Dr. Anderson from Dana-Farber, at 5:35 he says the novel agents can kill myeloma cells bound to the bone marrow, but high dose alkylators cannot. So I agree 100% with the point that Auto is unnecessary for a patient that gets MR from Induction.
http://myeloma.org/ArticlePage.action?tabId=22&menuId=163&articleId=3295&aTab=-4&gParentType=link&gParentId=5510&parentIndexPageId=317
My only disagreement with you was that you put MR and IR in with sCR and CR and said patients with VGPR could have as good of an outcome as a patient with MR. There is a big improvement in outcomes when a patient gets MR or IR. IMO MR or IR should be the initial therapy goal for all patients.
Mark
-
Mark
Re: Precision Medicine will be in Action @ ASCO 2012
Congrats Mark on your one year anniversary of MR and basically being in a great remission! That is a real landmark and hope you have many more years like that ahead of you! I wouldn't know if I was in aN MR, but certainly being in a CR for two years is reassuring, as i am now. What tests exactly were used to determine your MR? Did that involve another BMB? I would like to know about it, especially if it were determined by just a blood test!
-
Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Precision Medicine will be in Action @ ASCO 2012
Hi Mark!!
Congrats!! On the one year...what a wonderful reason for such a good mood. I was watching playoffs last night and can't believe Heat let Celtics win, so I am just now seeing this. Very happy for you...will return later to discuss trials in post.
yes, Yes, YES!!! dare to dream....
Way to GO!! woooHooo!!
Congrats!! On the one year...what a wonderful reason for such a good mood. I was watching playoffs last night and can't believe Heat let Celtics win, so I am just now seeing this. Very happy for you...will return later to discuss trials in post.
yes, Yes, YES!!! dare to dream....
Way to GO!! woooHooo!!
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Precision Medicine will be in Action @ ASCO 2012
Congratulations on your test results, Mark. That's great news. I hope the MR continues to hold at least until the 30th birthday of your youngest great, great granddaughter. 
-
TerryH
Re: Precision Medicine will be in Action @ ASCO 2012
Hi Mark, awesome news! Also, thanks for all of your postings and exchanges with other posters. They really contribute a lot to the forum. Terry L.
-
terryl1 - Name: Terry
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August 10, 2011
- Age at diagnosis: 49
28 posts
• Page 1 of 3 • 1, 2, 3
Return to Treatments & Side Effects