Researchers Identify Factors That Predict Long-Term Survival In Newly Diagnosed Myeloma Patients
Results from a recent French study identified several factors that predict long-term survival of patients newly diagnosed with multiple myeloma. These prognostic factors include the absence of three key chromosomal abnormalities, low beta-2 microglobulin levels in the blood, and younger age.
The three key chromosomal abnormalities that were absent in patients who survived longer were a gain in chromosome 1 (called 1q gain), a translocation from chromosome 4 to 14 (called t(4;14)), and a deletion in chromosome 17 (called del(17p)). Patients who lived longer were also younger than 55 years of age and had blood beta-2 microglobulin levels below 5.5 mg/L.
“There are several important observations [from this study],” noted Beacon Medical Advisor Dr. Peter Voorhees, an assistant professor of hematology and oncology at the University of North Carolina in Chapel Hill, who was not involved in the study. “Firstly, this study reaffirms the prognostic importance of gains on the long arm of chromosome 1. [In addition,] the absence of any high-risk features identifies a group of patients, representing 20 percent of all patients, who have an excellent long-term outcome,” he said.
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Based on their findings, the French researchers recommend that 1q gain be added to the panel of risk factors that newly diagnosed myeloma patients are screened for. Both t(4;14) and del(17p) are already on the regular testing panel.
The researchers point out, however, that the patients included in the study did not receive initial treatment with novel agents such as thalidomide (Thalomid), Revlimid (lenalidomide), or Velcade (bortezomib). Other studies have suggested that some novel drugs can overcome poor prognosis associated with certain chromosomal abnormalities.
“Although patients that were included in this analysis received ‘old school’ induction therapy, it stands to reason that the prognostic model that they have developed would be applicable to modern-day therapy,” said Dr. Voorhees. “Patients identified as good risk based on this model should do even better with current therapy,” he added.
Previous studies have shown that the presence of chromosomal abnormalities can have a negative effect on myeloma prognosis (see related Myeloma Beacon news).
Elevated levels of beta-2 microglobulin in the blood have also been associated with increased disease severity (see related Myeloma Beacon news).
However, the effects of these factors on long-term survival of myeloma patients remain poorly understood because there are very few studies that have followed patients over extended periods of time.
In the current study, the French investigators addressed this problem by retrospectively analyzing genetic and other risk factors in patients who had enrolled in myeloma trials about eight years ago. They then tested if these risk factors could be used to predict long-term survival.
The researchers included 520 patients in their analysis, all of whom had enrolled in two French trials. All patients were younger than 66 years of age and were newly diagnosed with multiple myeloma at the start of the trials.
The trial participants had received induction therapy with vincristine (Oncovin), doxorubicin (Adriamycin), and dexamethasone (Decadron), followed by high-dose melphalan (Alkeran) plus stem cell transplantation.
The median follow-up period was about 7.5 years.
The researchers found that older age (above 55 years), higher beta-2 microglobulin levels (above 5.5 mg/L), low red blood cell counts, and deletions in chromosomes 13 and 17, and t(4;14) had a negative effect on progression-free survival.
They also found that older age, higher beta-2 microglobulin levels, t(4;14),del(17p), and 1q gains had a negative effect on overall survival.
According to the researchers, the fact that the 1q gain impacted overall but not progression-free survival suggests that this abnormality becomes more important as the disease progresses.
Taking these risk factors into account, the researchers developed a mathematical model that could predict overall survival based on the number of risk factors a patient carried.
The median overall survival for all study participants was 7.3 years.
Patients without any risk factors (20 percent of the patients included in the analysis) had the longest survival time (not yet reached).
The median overall survival time was 9.5 years for patients with one risk factor (44 percent) and 5.6 years for patients with two risk factors (26 percent).
Patients with more than two of these risk factors (11 percent) had the shortest median overall survival time of less than three years.
Statistical analysis also showed that t(4;14) had the worst impact on overall survival time.
For further information, please see the study in the Journal of Clinical Oncology (abstract).
Related Articles:
- Importance Of Factors Affecting Multiple Myeloma Survival Changes With Patient Age
- Recently Diagnosed Myeloma Patients Very Likely To Have Low Testosterone Levels, Study Finds
- Early Use Of Radiation Therapy Associated With Shorter Survival In Multiple Myeloma
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
Thanks for the article Sruti. These results seem to be much better than previously published results, at least to me as an average reader!
This article is so meaningless and yet it could frighten some patients (e.g. the elderly) since they are doomed to a shorter median life than younger patients. Surprise.Surprise. As Mark Twain says "there are lies, damned lies and statistics". Using a median as measure of central tendency in a correlation study is a perfect example. It the "viability" between patients that is important, the tail on the distributions, etc. I would encourage any MM patient who is going to read about survivability to first, read the excellent but short essay by the scholar Jay Gould, entitled "The MEDIAN is NOT the MESSAGE". Here is the link
http://cancerguide.org/median_not_msg.htm
Gould wrote this after he was diagnosed with mesothelioma and given a short "median" life sentence and how he dealt with it.
I think it is a must read for anyone, particularly a newly diagnosed MM patient faced with frightening prognostications from the cancer literature. See if you agree and if you do pass along the essay to new patients.
@Gary - What do you suggest myeloma patients do? Bury their heads in the sand and not read anything that has survival numbers in it?
And what should publications like the Beacon do? Not report anything and just say, repeatedly, "Don't worry Mr. and Ms. Myeloma Patient. All the survival data you'll find anywhere is meaningless and has no bearing on your particular case because you are just soooo unique and soooo special So ignore all the new research about what might affect your survival. Sure, it might be useful to know, since it might affect treatment decisions. But leave all that to your myeloma specialist. Only people with a "Dr." in front of their name who have been taught the special super-super-secret doctor handshake can really understand the deep hidden meaning in survival statistics."
Or do you want publications like the Beacon to start reporting second and third moments of the sample distributions along with details about whether the distributions can be characterized as normal, log-normal, or something else?
Be serious.
Yes, medians are only part of the message. Yes, it's a good idea to remind people of that now and then.
But to call an article like this "meaningless" is just plain wrong. I found the article useful and interesting, in part because it was honest about potential limitations of the study it discusses.
I concur with Terry!
Hi TerryH and Suzie Rose. Did you read the article by Jay Gould? I guess that is what I wanted patients to do and I didn't do a good job. As a practicising statistician I worry about the use of central tendencies and non designed data to draw conclusions. When I was diagnosed with level II Myeloma and given four years to live I heard only the "four" years as Jay Gould did.
I attended a MM workshop this weekend. I suspect that is what got me all wound up. The presenting doctors claimed that there was no "scientific evidence", read "statistical evidence", that maintenance had any effect on survivability based on the "median". Further that there was no evidence of improved survivability following stem cell transplants.
Don't you think that perhaps another criterion is needed than the Median? How about quality of life?
Statisticians have a tendency to take a set of data and relate any number of factors to some measured variable. Sometimes this works well. But if the information isn't there they still come up with conclusions. They have an equation Garbage In= Garbage Out.
Don't you think the conclusion that earlier diagnosed patients will live longer than older diagnosed patients is even a little trite?
I am very sorry that you were offended by my statement that the article was wrong. But that is how I feel about correlation
I was only trying to protect the MM patients not familiar with the technology. They have enough to worry about.
If you read the essay by Gould and still feel I am off base for warning about the use of median. I will back off the topic of statistics until I pass away (which based on the median will be 1.756 years from now).
Hi Gary, Thanks for the link to the great article by Jay Gould. It was inspiring and I think I should read some of his books now! It's important not to get too stressed out by statistics, or anything else that we have not much control over anyways.
Hi Gary,
I must admit I did not read Gould, and tried to do so now, but link is not working.
"The presenting doctors claimed that there was no “scientific evidence”, read “statistical evidence”, that maintenance had any effect on survivability based on the “median”. Further that there was no evidence of improved survivability following stem cell transplants.
Don’t you think that perhaps another criterion is needed than the Median? How about quality of life?"
I certainly agree with you about QOL.
Scientifically, as you know, there have to be criteria that allow for comparision and consistency between studies and 'median' allows for that. Perhaps, patients become dejected when they learn that autoSCT do not result in improved survival? It can be jarring to learn that the HDT, side effects and often long recovery from obliterating the immune system do not result in an improved outcome in terms of survival. In that sense, it can be disheartening to learn that it is QOL that should be the highest priority as survival has not been shown to be a realistic goal?
OTOH, what would it take to demonstrate 'improved survival' in a basically geriatric population? How do we even know the expected lifetime expectancy for the group? We can calculate it based on year of birth for the population as a whole, but the population that gets MM can not reasonably be expected to have that same overall survival, no? Simply based on them having the disease. So, what parameters should we use as study endpoints when it comes to novel agents vs. conventional therapy and survival?
Should we look at PFS? Is PFS the really important measure and extending that independent of OS is the better criterion as it would encompass QOL?
"Don’t you think the conclusion that earlier diagnosed patients will live longer than older diagnosed patients is even a little trite?"
Only if we are comparing same ages.
Younger (50-60) patients diagnosed late typically live longer than older( 60-70) patients diagnosed early.
Also, we have to have comparative criteria for 'early diagnosis' does that mean you are ISS one vs ISS three..if so that has not been found to necessarily correlate with living longer either.
MM is such a heterogeneous disease that patients can have significant disease multiple lesions and have a longer PFS than a patient who has cytogenetic abnormalities and is ISS one. The disease is very confounding when it comes to staging and the aggressiveness of the disease. A 70 y.o. male with diffuse bone lesions, high B2microglobulin can have longer PFS than a 50 y.o. patient with low B2microglobulin and only 3 lesions, but they have 17p and gain of 1q..so their PFS is shorter even IF they reach CR with induction therapy.
LOL, at your median demise. I do hear you about statistics, and understand why you had an issue. I guess I took it for what it meant, in that 50% did better than the median...hope springs eternal.
Suzie: Just google "The Median is not the message Gould". Then let me know what you think.
Gary,
I agree that we need to be careful in how statistics, particularly the median, are used to characterize progression-free and overall survival (PFS & OS). However, there is some value if enough data is provided and used and interpreted correctly. For example, if we're only told the median survival is 3 years, it's not too useful since as you say, we tend to fixate on the 3 years and have no other useful data to go on. However, if the information is used for comparison purposes, it has some value. Case in point for this article - they report a statistically significant difference in PFS and OS based on the different prognostic factors. While we should be cautious in using the actual values, the differences between them (9.5 vs 5.6 vs. 3) do provide an indication of the relative imporvement in OS. The information I'd like to see would be the distribution of the data, since it provides an indication of how PFS or OS extend to either side of the median (actually, mean and standard deviation or variance would be nice).
hi all,
why does one need to care about median life along with worrying about anything. living today is all i personally care about. having an incurable disease does not stop me from living the life that i have left. numbers and words associated with this cancer are just that, numbers and words. all said this does not stop me from being I formed. often when I am asked how long do I have left I respond by saying 'the doctors have given me till the end of the year. I just don't know which year.' this statements gets a greater initial stun then laugh towards the end of the calendar year. I have bad days and good days but until my time arrives I will at least try to enjoy and be thankful for each day. hope you all concur with a joyful day.
jim
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