Study Identifies Factors Linked To Longer Survival Among Myeloma Patients Receiving Stem Cell Transplants
Indian researchers recently identified several factors linked to improved survival among multiple myeloma patients who have undergone stem cell transplantation.
These factors included albumin levels at diagnosis and the achievement of a response – particularly a complete response – after transplantation.
Patients who achieved a complete response after transplantation, for example, had a median overall survival of 17 years.
The use of novel agents as initial treatment was also associated with improved overall survival.
Based on their findings, the study investigators recommend using initial therapy prior to transplantation that aims to achieve the highest response rate possible. This approach, they argue, could increase the rate of complete responses post transplantation, thereby lengthening patient survival.
According to the study authors, future research into stem cell transplantation should focus on the timing of the transplant and the identification of patients who are at a higher risk for relapse.
High-dose chemotherapy followed by autologous stem cell transplantation (i.e., transplantation using a patient’s own stem cells) is a common treatment option for multiple myeloma patients age 65 years and under.
Prior studies have shown that patients who achieve a complete response after stem cell transplantation experience improved overall survival (see related Beacon news).
The purpose of the current study was to confirm and identify additional factors that may predict survival outcomes in patients receiving an autologous stem cell transplant.
Study investigators retrospectively evaluated records from 170 multiple myeloma patients who had received a stem cell transplant at their cancer center between 1990 and 2010.
The median patient age was 52 years; 39 percent had received novel agents, such as thalidomide (Thalomid), Velcade (bortezomib), or Revlimid (lenalidomide), as their initial therapy.
Of the 170 patients included in the analysis, 78 percent had responded to their initial treatment.
Patients received the transplant within a median of 10 months of their diagnosis.
The majority of patients received high-dose chemotherapy with 200 mg/m2 of melphalan (Alkeran) as part of their transplant. Lower dosages of melphalan (120 mg/m2 to 150 mg/m2) were administered to patients with impaired kidney function.
Patients started producing blood cells a median of 11 days after the transplant.
Overall, 91 percent of patients responded to the transplant; 45 percent of patients achieved a complete response, 25 percent a very good partial response, and 21 percent a partial response. According to the study investigators, these results are similar to those of other recent studies.
The investigators found that a patient’s pre-transplant disease status, response to initial treatment, and time from diagnosis to transplant were factors that significantly affected their response to the transplant.
After a median follow-up time of 7 years, the median event-free survival was 3.4 years, and the median overall survival was 7.1 years.
The investigators found that albumin levels above 3.4 g/dL at diagnosis and the achievement of a response, in particular a complete response, after transplant were significant predictors of improved progression-free and overall survival.
Albumin is the most abundant protein in human blood plasma. A patient's albumin level is one of the factors used in the International Staging System to determine disease stage.
Patients with albumin levels greater than 3.4 g/dL, for example, had a median overall survival of 11.7 years versus 6.6 years for those with albumin levels equal to or less than 3.4 g/dL. Patients who achieved a complete response after transplantation had a median overall survival of 17 years versus about 3.8 years for those who did not.
In addition, the use of novel agents as initial treatment was associated with improved overall and event-free survival survival.
Median event-free survival was 4.2 years among patients treated initially with novel agents. It was 2.3 years among patients treated initially with the combination therapy known as VAD -- vincristine, doxorubicin (Adriamycin), and dexamethasone (Decadron). It was only 1.3 years among patients treated initially with regimens including either melphalan or cyclophosphamide (Cytoxan).
The median overall survival has not yet been reached for patients in the study who received novel agents as initial therapy; it was 7.1 years for patients initially treated with the VAD regimen, and 2.7 years for those initially treated with regimens including either melphalan or cyclophosphamide.
For more information, please see the study in Clinical Lymphoma, Myeloma & Leukemia (abstract).
Related Articles:
- Stem Cell Transplantation May Be Underutilized In Multiple Myeloma Patients In Their 80s
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Selective Digestive Decontamination May Reduce Risk of Infection In Myeloma Patients Undergoing Autologous Stem Cell Transplants
- Importance Of Factors Affecting Multiple Myeloma Survival Changes With Patient Age
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
That is an interesting study out of the All India Institute of Medical Sciences, New Delhi. A median overall survival of 17 years post transplant, with patients who had good responses and also were treated with novel agents, is impressive.
The article makes the statement ".. pre-transplant disease status, response to initial treatment, and time from diagnosis to transplant were factors that significantly affected their response to the transplant." However, the article didin't include how the "time from diagnosis to transplant" affected response. This is of particular interest to me since I decided to go with the CRD trial and avoid the SCT until I relapse.
I did check out the referenced abstract, and it did mention that transplant within 12 months typically resulted in better survival. I wonder whether the transplant would still provide the increased survival if you've reached a complete response (molecular in my case) on the novel agents?
Hi Kevin, I read somewhere that only a small percentage of the patients on the carfilzomib trials chose to do an ASCT immediately following their chemotherapy. I am sure that all of you will be followed closely, since you have tried out a new myeloma drug. It is indeed so interesting to be able to follow all of these studies on the Beacon...there is no way I could look up all of this info on my own! Even for those of us who have had the 'novel' agents, the data is not all in yet on as to how we are doing into the future!
Li writes:
"Of the 170 patients included in the analysis, 78 percent had responded to their initial treatment."
Ok, but how many patients achieved a Complete Response?
"Patients with albumin levels greater than 3.4 g/dL, for example, had a median overall survival of 11.7 years versus 6.6 years for those with albumin levels equal to or less than 3.4 g/dL"
What percent of patients, in the analysis, had albumin levels greater than 3.4g/dl. ?
What percent of MM patients, overall have albumin levels greater than 3.4g/dl?
Are albumin levels indicative of the stage of myeloma when the patient presents, as the myeloma cells crowd out rbc's as well as albumin in the marrow?
Normal albumin levels are 3.43 - 4.84, so it appears he's indicating low albumin levels are an indicator of potnetially shorter survival. Mine hovered between 3.5 and 3.8 when first diagnosed (I guess my wife and I can go ahead and plan our 40th anniversay now). I agree with your (sensed) frustration at how this data is presented - it teases, but there's a lot of underlaying information needed to interpret it correctly.
Li writes:
"The purpose of the current study was to confirm and identify additional factors that may predict survival outcomes in patients receiving an autologous stem cell transplant."
Abstract conclusion:
"Outcome after ASCT is better for myeloma patients with pretransplant chemosensitive disease and those who achieve CR after transplant."
The study did not identify additional factors that predict survival in the conclusion.
This study is a retrospective analysis of only SCT patients. How did patients who achieved a CR prior to transplant who did not receive a ASCT compare in terms of OS to those who did?
It seems that the study is saying that OS was dependent on the depth of response being PR, VGPR or CR in terms of median survival. This is data that is well known.
How does the data add to what we presently know about the depth of response to chemotherapy being indicative of length of survival, at present?
"Patients received the transplant within a median of 10 months of their diagnosis."
Given the length of OS being 12 years, this data was prior to the new agents available today.
"The investigators found that a patient’s pre-transplant disease status, response to initial treatment, and time from diagnosis to transplant were factors that significantly affected their response to the transplant."
Where these factors significant independently or co-dependent? Which factor was the most significant? Was response to initial treatment the most significant factor, independent of time from diagnosis to transplant?
Data at the Myeloma Beacon shows outcomes from early or late HDT are not dependent on time from initial diagnosis:
http://www.myelomabeacon.com/news/2011/10/31/study-finds-early-and-delayed-stem-cell-transplants-have-comparable-efficacy-in-newly-diagnosed-multiple-myeloma-patients/
Yes, it seems they are saying that normal albumin levels have better overall survival. Not sure why that would be news.
I agree your 40th will be a great celebration, until you reach your 50th.
Here is an article from the Beacon regarding how low albumin levels are indicative of disease severity.
http://www.myelomabeacon.com/news/2009/11/29/serum-albumin-levels-indicate-severity-of-multiple-myeloma/
I just checked back on some of my lab results and the normal range for serum albumen here is from 35 - 53 (as usual, multiply by ten). i think that what I found to be intriguing about the article is the news of a study from an Indian source. Such an international type of posting and of course of interest to people in that country too.
Lots of great discussion and questions here.
We'll try to clarify a few things.
As the above article makes clear, the study being discussed focuses on factors associated with longer survival among patients who first had initial anti-myeloma therapy, then underwent high dose chemotherapy followed by an autologous stem cell transplant.
The study does not include patients who did not have a stem cell transplant. Nor did the study specifically delay the time of transplant of some patients, and not others.
Thus, the study cannot speak directly to current controversies such as whether early or late stem cell transplantation is better in terms of treatment outcomes, or whether transplantation significantly improves survival in patients treated intensively with novel agents.
Although many of the results in this study have been seen elsewhere in other studies, not all of our readers will be familiar with those studies, and this study helpfully adds to the literature on factors associated with longer survival in myeloma patients who have undergone transplantation.
That is why The Beacon decided to report the results found by the Indian researchers.
The factors reported in the above article as being associated with longer survival were those that showed a statistically significant link to longer survival **taking into account a wide range of potential factors affecting survival**.
In other words -- and this is more for those who are statistically inclined -- the factors emphasized in the article are those which were statistically significant in the context of a *multivariate* analysis.
There were, of course, other factors -- such as the stage of a patient's myeloma -- that were associated with longer survival in simple one-on-one correlations. But controlling for all variables at once, the variables emphasized in the article were the ones significantly associated with longer survial.
Now, to answer a few questions ...
1. Of the 170 patients in the study, 39 percent received initial treatment with novel agents. Although the study includes patients who were diagnosed as long ago as 1990, it also includes patients diagnosed as late as June 2010.
2. Pre-transplant (after only their initial therapy), 14 percent of the patients achieved a complete response. Post-transplant, the share of patients who had achieved complete response increased to 45 percent.
3. Sixty-six (66) percent of the patients had serum albumin levels greater than 3.4 g/dL.
4. The median interval from diagnosis to transplant was 10 months. The mean time ws 15.2 months. The range was 3 to 128 months.
5. Patients who had a transplant within one year of diagnosis had a median overall survival of 10 years. Those who had a transplant more than one year after diagnosis had median survival of 5 years.
One other interesting point is that all patients in the study received maintenance therapy after their transplant. Until the end of 2001, the maintenance therapy was interferon injected subcutaneously three times a week. Since 2002, the maintenance therapy has been thalidomide 50 mg daily for one year or more.
Another important factor is the average age in this study was 52, well below the average age for myeloma patients. It has been shown in the past that younger patients live longer, so that certainly has to be considered a factor in these results.
I wonder if there is any explanation for the finding that median event-free survival and overall survival are much lower for patients initially treated with regimens including either melphalan or cyclophosphamide, and how it squares with the finding that event-free and overall survival were best for patients treated with novel agents. Where does this leave patients whose initial treatment included either melphalan or cyclophosphamide and a novel agent? I was initally treated with CyBorD (cyclophosphamide, Bortezomib, and dex) so this part of the report lept off the page at me.
" Patients who achieved a complete response after transplantation had a median overall survival of 17 years versus about 3.8 years for those who did not."
I may not be as far along the "technical curve" as some of you who've already commented so please forgive my lack of understanding, perhaps, when I ask how suddenly there are SCT patients in India who are achieving a median OS of 17 years when here in the U.S. the expected median OS is more like 5-7 years...what am I missing? Maybe they're using Curcumin rather thab Calfilzomib?
Thanks,
Steve
Thanks for the additional comments everyone.
@SueV - You are correct. The patients in this study were younger than you would see in a randomly selected group of myeloma patients. However, that's partly because all the patients in the study received transplants, and transplants even today are typically carried out in patients under the age of 65 to 70.
@Holt - The melphalan- and cyclophosphamide-containing treatment regimens mentioned in the study did not include CyBorD. Instead, they were two older regimens that did not include any of the novel anti-myeloma agents, namely "VMCP" (vincristine, melphalan, cyclophosphamide, and prednisone), and "MP" (melphalan and prednisone]. So it's not clear that you need to be concerned.
@Steve Cochran - Yes, the 17-year median overall survival is certainly impressive. Bear in mind, though, that it is for the subgroup of patients who were in complete response after their stem cell transplants -- that is, patients who responded well to their treatment.
You can view the overall survival graphs for the different response-rate groups here:
http://ars.els-cdn.com/content/image/1-s2.0-S2152265012001693-gr1.jpg
You'll see that the overall survival line for the complete response group crosses the 50 percent mark at about 204 months, which is exactly 17 years.
Still, given that the 17-year survival number is so noteworthy, we have reached out to the lead author of the study to confirm it. We'll let you know what we hear back.
Thanks for the follow-up.
The Myeloma Beacon said: "@Steve Cochran – Yes, the 17-year median overall survival is certainly impressive. Bear in mind, though, that it is for the subgroup of patients who were in complete response after their stem cell transplants — that is, patients who responded well to their treatment."
Yes, but, there are many here in the west who have CR after SCT and we have nothing close to a 17 year median survial.
The Myeloma Beacon said: "You can view the overall survival graphs for the different response-rate groups here: http://ars.els-cdn.com/content/image/1-s2.0-S2152265012001693-gr1.jpg You’ll see that the overall survival line for the complete response group crosses the 50 percent mark at about 204 months, which is exactly 17 years."
The graph is unclear to me as it seems to only show that some unquantified number of MM patients passed the 17 year mark and therefore I have to wonder if the number of survivors is so low that that the chart really amounts to kind of statistical cherry-picking?
The Myeloma Beacon said: "Still, given that the 17-year survival number is so noteworthy, we have reached out to the lead author of the study to confirm it. We’ll let you know what we hear back."
Yes! Pleas do! Who knows...maybe some of us will be brushing up on our Hindi soon? Namaste.
Hi Steve,
The survival relationships you see in the graph are estimated using a statistical technique that draws on the survival data for the patients falling into each response category.
For the curve for the complete response patients, that means that the graph is estimated based on a fairly reasonable number of patients. In particular, as we mentioned in an earlier comment above, about 45 percent of the patients in the study achieved a complete response after their transplant transplant.
We'll let you know when we hear back from the authors of the study about the length of the median survival time for the complete response group.
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