Thanks, everyone, for all the additional comments on the ASH abstract.
I have a few quick clarifications and replies to points that have been made in the discussion.
First, I need to clarify a bit what I wrote earlier about what treatment patients in this trial will get at relapse if they did not get an early transplant. I checked the abstract, and it explicitly says that these patients are expected to get a transplant at relapse. "In the RVD arm, ASCT was planned at time of relapse." So, more so than I realized when I posted earlier, this is truly an early vs. late transplantation study (NOT a transplant versus no transplant study).
Second, some replies to individual comments:
@MikeB - Yes, the 88% overall survival rate is definitely very good. As for the rate of secondary cancers, I would have liked to see it expressed in a way that allowed for comparison with published rates from other studies (e.g., rates per year of treatment).
@Rneb - I don't think there is anyting outdated about the treatment regimens used in this trial. I believe that is why the trial results have been so highly anticipated. The induction regimen does, in fact, use a triplet (RVD), and it also uses the triplet for two cycles of consolidation. All patients in the trial also got Revlimid maintenance for two years.
This matches very well with the most common treatment regimens in the U.S. these days. Some might even consider the trial regimen a bit more "advanced" -- due to the RVD consolidation therapy -- than what is currently common in the U.S. Also, the trial regimen involves more novel agents than are commonly used for newly diagnosed patients in many European countries and elsewhere.
Separately, you write "soon to be released oral based medications, such as proteasome inhibitors and IMiDs" Are there any IMiDs that are NOT oral? All of the ones that I'm aware of -- thalidomide, Revlimid, and Pomalyst -- are oral. I'm also not aware of any new IMiDs expected to come to market in the near future.
@Mark11 - Thanks for the reminder regarding the frequency of transplantation among U.S. patients. JPC is correct, in part, that the rate probably should be considered perhaps twice what you reported, when you take into account which newly diagnosed myeloma patients are really "eligible" for a transplant. But it's still not as common as many believe. Good point.
It would be interesting to have a separate discussion about why people have the impression that the rate of transplantation is higher than it really is.
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Re: Initial results: key stem cell transplant clinical trial
Cheryl G, To answer your question about why people have the impression that transplants are more prevalent than they actually are: the overwhelming number of people who describe their experiences here in the forum seem to have gone the transplant route. My own impression until reading this thread was that it is normal procedure to have a transplant and that it is the rare patient who opts out.
Re: Initial results: key stem cell transplant clinical trial
Hi again,
Rneb raised a good point about the possibility that the results from this trial will be out of date by the time all the data are published. That possibility is something that I've thought about a lot. What's the point of doing this large, involved clinical trial if success with novel treatments keeps advancing faster than the results from this trial come in? What if the most common initial treatment triplet combo becomes Kyprolis / Pomalyst / dex instead of RVD before we have the results of this study? What if some monoclonal antibody treatment changes the game?
I don't have a great answer for you, Rneb. But here's how I think about it and reconcile my participation in this trial. This study is a snapshot in time, comparing two of the most common first line treatment modalities in use at the time the study began. Maybe they are 2008-2012 treatments, as you said. Maybe not. I tend to agree with Cheryl G that they still are the most common first line choices today in the US. Revlimid and Velcade also happen to be the first new novel/targeted agents to be commonly used. So I think it is important to compare Novel Only vs. Novel+SCT as this study does.
But treatments will advance (at least I sure hope they do) and the results of this study will be out of date sometime in the future because these treatments become "old technology." That's the way it is with all clinical trials. In fact, the researcher at my treatment center who is heading this clinical trial at the institution told me back in 2013 that he expects that auto SCTs will only rarely be used for multiple myeloma treatment in 10 years (from 2013). So the "shelf life" of this study may not be all that long. Nevertheless, I think the snapshot is important and hope that it will help guide doctors and patients for awhile.
I also should say that I doubt that the French results to be presented at ASH will change anyone's mind in the debate about early vs. late SCTs. We are seeing that even in the comments in this thread. Only a large difference one way or the other in OS will cause people to change their minds. Whether we'll see that still is the big question.
Mike
Rneb raised a good point about the possibility that the results from this trial will be out of date by the time all the data are published. That possibility is something that I've thought about a lot. What's the point of doing this large, involved clinical trial if success with novel treatments keeps advancing faster than the results from this trial come in? What if the most common initial treatment triplet combo becomes Kyprolis / Pomalyst / dex instead of RVD before we have the results of this study? What if some monoclonal antibody treatment changes the game?
I don't have a great answer for you, Rneb. But here's how I think about it and reconcile my participation in this trial. This study is a snapshot in time, comparing two of the most common first line treatment modalities in use at the time the study began. Maybe they are 2008-2012 treatments, as you said. Maybe not. I tend to agree with Cheryl G that they still are the most common first line choices today in the US. Revlimid and Velcade also happen to be the first new novel/targeted agents to be commonly used. So I think it is important to compare Novel Only vs. Novel+SCT as this study does.
But treatments will advance (at least I sure hope they do) and the results of this study will be out of date sometime in the future because these treatments become "old technology." That's the way it is with all clinical trials. In fact, the researcher at my treatment center who is heading this clinical trial at the institution told me back in 2013 that he expects that auto SCTs will only rarely be used for multiple myeloma treatment in 10 years (from 2013). So the "shelf life" of this study may not be all that long. Nevertheless, I think the snapshot is important and hope that it will help guide doctors and patients for awhile.
I also should say that I doubt that the French results to be presented at ASH will change anyone's mind in the debate about early vs. late SCTs. We are seeing that even in the comments in this thread. Only a large difference one way or the other in OS will cause people to change their minds. Whether we'll see that still is the big question.
Mike
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mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Initial results: key stem cell transplant clinical trial
Mike - As I was writing up my earlier posting, it occurred to me that the researchers who designed the IFM/DFCI trial did a good job picking an initial treatment regimen. The choice makes the results very relevant right now, and probably for several more years.
Yes, the results eventually will become dated. We'll be criticizing their relevance 5 or 10 years from now just as we criticize today the relevance of early vs. late transplantation trials from the 1990s and early 2000s. But I think the design of the IFM/DFCI trial shows some good forethought.
Mrozdav - I agree that, based on what you read here in the forum, you would think that early transplantation is much more common than it really is. I found this poll here in the forum, "Weekly Poll - Early vs Late vs No Transplant" (Feb 2014), that probably explains why we have that impression.
It's clear from those results that people here in the forum are much more likely to have an early transplant than your "average" myeloma patient, even if you would assume that everyone here is a young/transplant-eligible patient (which isn't the case).
Why is this? That's really the issue that I think is more interesting – and probably better discussed in a separate thread.
Yes, the results eventually will become dated. We'll be criticizing their relevance 5 or 10 years from now just as we criticize today the relevance of early vs. late transplantation trials from the 1990s and early 2000s. But I think the design of the IFM/DFCI trial shows some good forethought.
Mrozdav - I agree that, based on what you read here in the forum, you would think that early transplantation is much more common than it really is. I found this poll here in the forum, "Weekly Poll - Early vs Late vs No Transplant" (Feb 2014), that probably explains why we have that impression.
It's clear from those results that people here in the forum are much more likely to have an early transplant than your "average" myeloma patient, even if you would assume that everyone here is a young/transplant-eligible patient (which isn't the case).
Why is this? That's really the issue that I think is more interesting – and probably better discussed in a separate thread.
Re: Initial results: key stem cell transplant clinical trial
Updated results of the trial have been published recently:
Attal, M, et al, "Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma," The New England Journal of Medicine, Apr 6, 2017 (link to abstract)
ABSTRACT:
Methods: We randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients). Patients in both groups received maintenance therapy with lenalidomide for 1 year. The primary end point was progression-free survival.
Results: Median progression-free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone (50 months vs. 36 months; adjusted hazard ratio for disease progression or death, 0.65; P<0.001). This benefit was observed across all patient subgroups, including those stratified according to International Staging System stage and cytogenetic risk. The percentage of patients with a complete response was higher in the transplantation group than in the RVD-alone group (59% vs. 48%, P=0.03), as was the percentage of patients in whom minimal residual disease was not detected (79% vs. 65%, P<0.001). Overall survival at 4 years did not differ significantly between the transplantation group and the RVD-alone group (81% and 82%, respectively). The rate of grade 3 or 4 neutropenia was significantly higher in the transplantation group than in the RVD-alone group (92% vs. 47%), as were the rates of grade 3 or 4 gastrointestinal disorders (28% vs. 7%) and infections (20% vs. 9%). No significant between-group differences were observed in the rates of treatment-related deaths, second primary cancers, thromboembolic events, and peripheral neuropathy.
Conclusions: Among adults with multiple myeloma, RVD therapy plus transplantation was associated with significantly longer progression-free survival than RVD therapy alone, but overall survival did not differ significantly between the two approaches. (Supported by Celgene and others; IFM 2009 Study ClinicalTrials.gov number, NCT01191060
Attal, M, et al, "Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma," The New England Journal of Medicine, Apr 6, 2017 (link to abstract)
ABSTRACT:
Methods: We randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients). Patients in both groups received maintenance therapy with lenalidomide for 1 year. The primary end point was progression-free survival.
Results: Median progression-free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone (50 months vs. 36 months; adjusted hazard ratio for disease progression or death, 0.65; P<0.001). This benefit was observed across all patient subgroups, including those stratified according to International Staging System stage and cytogenetic risk. The percentage of patients with a complete response was higher in the transplantation group than in the RVD-alone group (59% vs. 48%, P=0.03), as was the percentage of patients in whom minimal residual disease was not detected (79% vs. 65%, P<0.001). Overall survival at 4 years did not differ significantly between the transplantation group and the RVD-alone group (81% and 82%, respectively). The rate of grade 3 or 4 neutropenia was significantly higher in the transplantation group than in the RVD-alone group (92% vs. 47%), as were the rates of grade 3 or 4 gastrointestinal disorders (28% vs. 7%) and infections (20% vs. 9%). No significant between-group differences were observed in the rates of treatment-related deaths, second primary cancers, thromboembolic events, and peripheral neuropathy.
Conclusions: Among adults with multiple myeloma, RVD therapy plus transplantation was associated with significantly longer progression-free survival than RVD therapy alone, but overall survival did not differ significantly between the two approaches. (Supported by Celgene and others; IFM 2009 Study ClinicalTrials.gov number, NCT01191060
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
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