Great discussion - very informative.
Perseverance,
Thanks for two informative posts. I just wanted to show you a statistic that backs up your point that depth of response is important toward moving us toward a cure. I have a high-risk form of the disease and did a full allogeneic transplant in my first remission, so I read more about allos than most multiple myeloma patients. The allo is certainly not something that most multiple myeloma patients can or will do because of the risks.
Here is a link to a paper about allos, and this shows just how important molecular remissions are:
Gahrton, G, and Björkstrand, B, "Allogeneic Transplantation In Multiple Myeloma," Haematologica, Sep 2008 (full text of article)
Excerpt:
"Another study found that in 48 patients who obtained a hematologic remission following allogeneic transplantation, 16 (33%) obtained durable PCR-negativity after transplantation, while 13 (27%) remained persistently PCR-positive, and 19 (30%) showed a mixed pattern. The cumulative risk of relapse at 5 years was 0% for PCR-negative patients, 33% for PCR-mixed patients and 100% for PCR-positive patients. These studies show that molecular remission is more common after allogeneic transplantation and that molecular remission predicts a longer relapse-free survival."
I am sure you have seen survival curves for patients that do allogeneic transplants. They fall quickly due to the treatment-related mortality (TRM), but they usually start to flatten in the 3-5 year range. For those patients in the PCR- negative group in the study above, they may be in "lifelong remission". Hopefully they will find a way to make the allo safer or get our own immune systems to recognize the cancer as foreign and destroy the minimal residual disease (MRD).
Have a Great Weekend,
Mark
Forums
Re: Are CR and PFS suboptimal surrogate endpoints?
Hi Mark,
There were 2 recent randomized studies that showed a lack of correlation between depth of response and overall survival.
Dr Rakjkumar cites both of them in the Blood article when he discusses the myth of complete response:
Harousseau JL, Attal M, Avet-Loiseau H, et al., "Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 Phase III trial," Journal of Clinical Oncology, 2010 (full text of article)
Ludwig H, Hajek R, et al, "Thalidomide dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma," Blood. 2009;113(15):3435-3442 (full text of article)
There were 2 recent randomized studies that showed a lack of correlation between depth of response and overall survival.
Dr Rakjkumar cites both of them in the Blood article when he discusses the myth of complete response:
Harousseau JL, Attal M, Avet-Loiseau H, et al., "Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 Phase III trial," Journal of Clinical Oncology, 2010 (full text of article)
Ludwig H, Hajek R, et al, "Thalidomide dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma," Blood. 2009;113(15):3435-3442 (full text of article)
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Are CR and PFS suboptimal surrogate endpoints?
Suzierose,
In the context that Dr. Rajkumar is speaking, I agree that complete response (depth of response) likely does not correlate to better overall survival. Those studies refer to patients that did not do allogeneic transplants. An autologous stem cell transplant is nothing more than a high dose of chemotherapy, most commonly 200 mg/m2 of Melphalan, although a mix of Busulfan/Melphalan/Velcade may be superior (see this ASH 2010 meeting abstract).
An auto can potentially improve depth of response short term, but it does not have the long-term (or short term) affect of an allo. The current multiple myeloma drugs / autos do not address the real problem multiple myeloma patients have - the immune system is supposed to kill things that are dangers to the body. Unfortunately, ours not only fail to attack the myeloma, it helps them survive (related article in Cancer Cell)
An allo puts a new immune system in the patient, and hopefully the immune system will attack the myeloma cells. The paper that I highlighted in my above post also contains this sentence about another small study:
"In three of the allogeneic transplants, molecular remission occurred more than 3 years after the transplant, while late molecular remissions were not seen in autologous transplant recipients, indicating a GVM effect in the allogeneic transplants."
That last sentence is showing patients that are no longer taking chemo having their new immune systems killing myeloma. That is why depth of response matters in allos, but does not correlate to better overall survival in patients that do not do allo transplants. Myeloma patients do not have Revlimid, dexamethasone, or melphalan deficiencies. Therefore, taking more of those drugs does not necessarily lead to a greater OS. I would think those 3 patients in the above study have a very small chance of relapse. Their new donor immune systems have clearly identified the myeloma cells as dangers and killed them. Also, the numbers in my above post clearly show the importance of molecular remissions after allos.
That is why I did an allo in my first remission. The chemo and the donor T cells I received during the allo consolidated my response to my induction - I am now in stringent complete response (sCR). Hopefully the new immune system will maintain that response (through vraft vs. myeloma affect). When an allo works, those patients have a chance at the longest remission without using as much chemo over time as most multiple myeloma patients that do not do allos. Though I did use a LOT of chemo my first 8 months after diagnosis!
I hope that answers your question. By the way, I agree with just about everything Dr. Rajkumar wrote in that paper since most multiple myeloma patients do not do allos.
Mark
In the context that Dr. Rajkumar is speaking, I agree that complete response (depth of response) likely does not correlate to better overall survival. Those studies refer to patients that did not do allogeneic transplants. An autologous stem cell transplant is nothing more than a high dose of chemotherapy, most commonly 200 mg/m2 of Melphalan, although a mix of Busulfan/Melphalan/Velcade may be superior (see this ASH 2010 meeting abstract).
An auto can potentially improve depth of response short term, but it does not have the long-term (or short term) affect of an allo. The current multiple myeloma drugs / autos do not address the real problem multiple myeloma patients have - the immune system is supposed to kill things that are dangers to the body. Unfortunately, ours not only fail to attack the myeloma, it helps them survive (related article in Cancer Cell)
An allo puts a new immune system in the patient, and hopefully the immune system will attack the myeloma cells. The paper that I highlighted in my above post also contains this sentence about another small study:
"In three of the allogeneic transplants, molecular remission occurred more than 3 years after the transplant, while late molecular remissions were not seen in autologous transplant recipients, indicating a GVM effect in the allogeneic transplants."
That last sentence is showing patients that are no longer taking chemo having their new immune systems killing myeloma. That is why depth of response matters in allos, but does not correlate to better overall survival in patients that do not do allo transplants. Myeloma patients do not have Revlimid, dexamethasone, or melphalan deficiencies. Therefore, taking more of those drugs does not necessarily lead to a greater OS. I would think those 3 patients in the above study have a very small chance of relapse. Their new donor immune systems have clearly identified the myeloma cells as dangers and killed them. Also, the numbers in my above post clearly show the importance of molecular remissions after allos.
That is why I did an allo in my first remission. The chemo and the donor T cells I received during the allo consolidated my response to my induction - I am now in stringent complete response (sCR). Hopefully the new immune system will maintain that response (through vraft vs. myeloma affect). When an allo works, those patients have a chance at the longest remission without using as much chemo over time as most multiple myeloma patients that do not do allos. Though I did use a LOT of chemo my first 8 months after diagnosis!
I hope that answers your question. By the way, I agree with just about everything Dr. Rajkumar wrote in that paper since most multiple myeloma patients do not do allos.
Mark
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Mark
13 posts
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