A second article published in today's issue of the New England Journal of Medicine summarizes the results of an Italian and Israeli study looking that looked at two key issues in the treatment of multiple myeloma: the role of transplantation, and the role of maintenance therapy.
Study Design
All patients in the study were newly diagnosed multiple myeloma patients 65 years of age or younger. Every patient in the study initially received four 28-day cycles of treatment with Revlimid and dexamethasone.
Patients were then randomly split into two groups.
One group received six 28-day cycles of treatment with melphalan, prednisone, and Revlimid (MPR).
The second group received tandem (two) autologous stem cell transplants, spaced four months apart. These transplants were done in the standard way, with high-dose melphalan administered first, followed by re-infusion of stem cells previously collected from the patient.
After the patients in these two groups were done with either MPR therapy or the tandem stem cell transplants, they once again were randomly split into two additional groups.
One group received Revlimid maintenance therapy until disease progression, while the other did not
Study Results
The investigators found that patients who underwent the tandem stem cell transplants had longer progression-free and overall survival than the patients who did not have the stem cell transplants.
Median progression-free survival was 43.0 months for patients who received the transplants versus 22.4 months for those who did not. The four-year survival rate was 81.6 percent in the transplantation patients versus 65.3 percent in those who did not receive transplants.
Revlimid maintenance therapy also improved progression-free survival. Patients who received Revlimid maintenance had a median progression-free survival of 41.9 months versus 21.6 months for those who did not receive Revlimid maintenance.
The three-year overall survival rate also was higher in patients who received Revlimid maintenance versus those who did not (88 percent versus 79.2 percent), but this difference was not statistically significant.
Additional Information
The abstract for this study is available here:
A Palumbo et al., "Autologous Transplantation and Maintenance Therapy in Multiple Myeloma," The New England Journal of Medicine, September 4, 2014.
As you might expect, the study has been discussed before here at The Beacon in various news articles covering major conferences. See, for example, the third study summarized in this article about last year's American Society of Hematology (ASH) meeting
"ASH 2013 Preview: Revlimid Maintenance Therapy For Multiple Myeloma," The Myeloma Beacon, December 2, 2013
The poster about the study that was presented at the ASH meeting can be viewed here, while a slide deck discussing the study that was presented at last year's American Society of Clinical Oncology meeting can be viewed here.
What Do You Think?
News articles about the results of this study have been published with headlines such as:
"Stem cell transplant with melphalan still preferred in myeloma"
"High-dose melphalan remains most effective option for newly diagnosed multiple myeloma"
Do you agree? What are your thoughts about the study?
Forums
Re: NEJM article on transplantation & Revlimid maintenance
I am not clear about the following statement:
"Revlimid maintenance also improved progression free survival. Patients who received Revlimid maintenance had a median progression-free survival of 41.9 months versus 21.6 months for those who did not receive Revlimid maintenance."
Does this observation apply only to patients that had the two transplants? Or does it apply whether or not the patient had the two transplants?
And of course do these findings differ according to risk status?
Thx.
"Revlimid maintenance also improved progression free survival. Patients who received Revlimid maintenance had a median progression-free survival of 41.9 months versus 21.6 months for those who did not receive Revlimid maintenance."
Does this observation apply only to patients that had the two transplants? Or does it apply whether or not the patient had the two transplants?
And of course do these findings differ according to risk status?
Thx.
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JiminSD
Re: NEJM article on transplantation & Revlimid maintenance
Thanks for your questions, Jim.
The comparisons in survival outcomes based on whether or not the patients had Revlimid maintenance were done as follows.
First, patients were separated into two groups for the analysis.
The first group included all patients that received Revlimid maintenance, regardless of whether or not they had transplants.
The second group included all patients who did not receive Revlimid maintenance, again regardless of whether or not they had transplants.
Then survival outcomes for these two groups were calculated and compared, as summarized in our posting above.
The same thing was done for comparisons based on transplant status. The authors created two groups -- patients who had transplants, and patients who did not -- disregarding the issue of Revlimid maintenance when creating those groups.
There does not appear to be any analysis in the main paper that takes into account the patient's risk status at diagnosis. We've not yet looked in detail at the supplementary data that are available for the study.
The comparisons in survival outcomes based on whether or not the patients had Revlimid maintenance were done as follows.
First, patients were separated into two groups for the analysis.
The first group included all patients that received Revlimid maintenance, regardless of whether or not they had transplants.
The second group included all patients who did not receive Revlimid maintenance, again regardless of whether or not they had transplants.
Then survival outcomes for these two groups were calculated and compared, as summarized in our posting above.
The same thing was done for comparisons based on transplant status. The authors created two groups -- patients who had transplants, and patients who did not -- disregarding the issue of Revlimid maintenance when creating those groups.
There does not appear to be any analysis in the main paper that takes into account the patient's risk status at diagnosis. We've not yet looked in detail at the supplementary data that are available for the study.
Re: NEJM article on transplantation & Revlimid maintenance
Stil a bit odd.
For example, isn't one interpretation that there is no positive gain to choosing a back to back transplant (over MPR) provided you follow a Revlimid maintenance program? In fact, doesn't choosing this non-transplantation route increase the median OS by more than 6 months compared with transplanted patients?
For example, isn't one interpretation that there is no positive gain to choosing a back to back transplant (over MPR) provided you follow a Revlimid maintenance program? In fact, doesn't choosing this non-transplantation route increase the median OS by more than 6 months compared with transplanted patients?
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JiminSD
Re: NEJM article on transplantation & Revlimid maintenance
There are basically four treatment sequences people in this study could have received.
1. Rd -> transplants -> Revlimid maintenance
2. Rd -> transplants -> no maintenance
3. Rd -> MPR -> Revlimid maintenance
4. Rd -> MPR -> no maintenance
where "Rd" = Revlimid and dexamethasone.
Here are the progression-free survival times (PFS) and 5-year overall survival rates (OS) for these four groups of patients.
Treatment sequence PFS 5-year OS
(months) (%)
1. Rd -> transplants -> Revlimid maintenance 54.7 78.4
2. Rd -> transplants -> no maintenance 37.4 66.6
3. Rd -> MPR -> Revlimid maintenance 34.2 70.2
4. Rd -> MPR -> no maintenance 21.8 58.7
Note that not all differences in the above table are statistically significant.
So, as one would have expected from our first summary of the paper's results, Revlimid maintenance improved both PFS and OS regardless of whether a patient received transplants or MPR after initial therapy with Rd.
Likewise, transplantation improved both PFS and OS regardless of whether one had went on to have Revlimid maintenance therapy or not.
It is true that continuous therapy with Rd, MPR, and Revlimid maintenance did provide a slight improvement in overall survival versus having Rd, transplants, and no maintenance.
However, the highest 5-year overall survival in the study was in the group that had treatment sequence 1, which included the tandem transplants and Revlimid maintenance.
Hope this clarifies things a bit.
1. Rd -> transplants -> Revlimid maintenance
2. Rd -> transplants -> no maintenance
3. Rd -> MPR -> Revlimid maintenance
4. Rd -> MPR -> no maintenance
where "Rd" = Revlimid and dexamethasone.
Here are the progression-free survival times (PFS) and 5-year overall survival rates (OS) for these four groups of patients.
Treatment sequence PFS 5-year OS
(months) (%)
1. Rd -> transplants -> Revlimid maintenance 54.7 78.4
2. Rd -> transplants -> no maintenance 37.4 66.6
3. Rd -> MPR -> Revlimid maintenance 34.2 70.2
4. Rd -> MPR -> no maintenance 21.8 58.7
Note that not all differences in the above table are statistically significant.
So, as one would have expected from our first summary of the paper's results, Revlimid maintenance improved both PFS and OS regardless of whether a patient received transplants or MPR after initial therapy with Rd.
Likewise, transplantation improved both PFS and OS regardless of whether one had went on to have Revlimid maintenance therapy or not.
It is true that continuous therapy with Rd, MPR, and Revlimid maintenance did provide a slight improvement in overall survival versus having Rd, transplants, and no maintenance.
However, the highest 5-year overall survival in the study was in the group that had treatment sequence 1, which included the tandem transplants and Revlimid maintenance.
Hope this clarifies things a bit.
Re: NEJM article on transplantation & Revlimid maintenance
Clarifies everything. Thank you. I did not have access to the full paper (and hence this breakdown) -- I only saw the information in the abstract.
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JiminSD
Re: NEJM article on transplantation & Revlimid maintenance
Please define PFS. When does the clock start ticking? And when does it stop? The day of the transplant? At a certain M-spike?
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coachhoke - Name: coachhoke
- When were you/they diagnosed?: Apri 2012
- Age at diagnosis: 71
Re: NEJM article on transplantation & Revlimid maintenance
Hi CoachHoke,
The progression-free survival numbers we listed above are median progression-free survival from the time of diagnosis.
The progression-free survival numbers we listed above are median progression-free survival from the time of diagnosis.
Re: NEJM article on transplantation & Revlimid maintenance
From time of diagnosis until what? Define progression please.
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coachhoke - Name: coachhoke
- When were you/they diagnosed?: Apri 2012
- Age at diagnosis: 71
Re: NEJM article on transplantation & Revlimid maintenance
Hi CoachHoke,
You may recall that we discussed this subject before in this forum thread,
"Survival and response rate definitions?", Beacon forum discussion started June 13, 2014.
As we mentioned in that discussion, there are a lot of details to the definition of disease progression to cover the wide range of cases that can occur.
However, for most patients, disease progression occurs when the patient either (a) experiences an increase in their M-spike of 25 percent (but the increase must be at least 0.5 g/dL), or (b) dies.
Technically, the definition of disease progression used in the NEJM study is based on older criteria for response rates and disease progression. The ones we mentioned in the discussion thread earlier in this posting are from 2011. The ones used in the NEJM study are from 2006. They are detailed in this paper,
"International uniform response criteria for multiple myeloma," Leukemia 2006.
and specifically this table.
You may recall that we discussed this subject before in this forum thread,
"Survival and response rate definitions?", Beacon forum discussion started June 13, 2014.
As we mentioned in that discussion, there are a lot of details to the definition of disease progression to cover the wide range of cases that can occur.
However, for most patients, disease progression occurs when the patient either (a) experiences an increase in their M-spike of 25 percent (but the increase must be at least 0.5 g/dL), or (b) dies.
Technically, the definition of disease progression used in the NEJM study is based on older criteria for response rates and disease progression. The ones we mentioned in the discussion thread earlier in this posting are from 2011. The ones used in the NEJM study are from 2006. They are detailed in this paper,
"International uniform response criteria for multiple myeloma," Leukemia 2006.
and specifically this table.
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