There is a new study out that looks at the impact of high-risk chromosomal abnormalities on the prognosis of newly diagnosed multiple myeloma patients.
The study was done by researchers at the Mayo Clinic, using data for more than 1000 myeloma patients diagnosed from 2005 to 2015. All patients in the study were treated with at least one "novel" myeloma therapy (an immunomodulator, such as Revlimid or thalidomide, or a proteasome inhibitor, such as Velcade) as part of their initial therapy.
The authors defined high-risk chromosomal abnormalities to be t(4;14), t(14;16), t(14;20) and del(17p). They also investigated the impact on prognosis of two different chromosome 13 abnormalities, monosomy 13 and del(13q).
There are two main findings of the study.
First, the authors found that the fewer high-risk abnormalities a patient had at diagnosis, the better the patient's prognosis. Patients with no high-risk abnormalities had the best prognosis; patients with one high-risk abnormality had the second-best prognosis; etc.
Second, the two chromosome 13 abnormalities have very different impacts on prognosis. Having monosomy 13 was associated with a poorer prognosis, while having del(13q) was correlated with a better prognosis.
There are tables and charts in the article that have actual survival numbers, and perhaps those can be discussed in further posts in this thread.
Note that the full text of the article can be read at the link below without any sort of subscription; it's an "open" article.
Here's the reference for the study:
Binder, M, et al, "Prognostic implications of abnormalities of chromosome 13 and the presence of multiple cytogenetic high-risk abnormalities in newly diagnosed multiple myeloma," Blood Cancer Journal, Sep 1 2017 (full text of article)
And here's the abstract
Fluorescence in situ hybridization evaluation is essential for initial risk stratification in multiple myeloma. While the presence of specific cytogenetic high-risk abnormalities (HRA) is known to confer a poor prognosis, less is known about the cumulative effect of multiple HRA. We studied 1181 patients with newly diagnosed multiple myeloma who received novel agents as first-line therapy. High-risk abnormalities were defined as t(4;14), t(14;16), t(14;20) and del(17p). There were 884 patients (75%) without any HRA and 297 patients (25%) with HRA, including 262 (22%) with one HRA and 35 (3%) with two HRA. The presence of one HRA (versus zero, hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.32–2.05, p<0.001) and the presence of two HRA (versus zero, HR 3.15, 95% CI 2.00–4.96, p<0.001) were of prognostic significance after adjusting for other prognostic factors. Abnormalities of chromosome 13 were of prognostic significance independent of the established HRA: Monosomy 13 (HR 1.27, 95% CI 1.04–1.56, P=0.022) and del(13q) (HR 0.48, 95% CI 0.28–0.81, P=0.006) with opposite effects. Patients with HRA experienced worse overall survival suggesting a cumulative adverse effect of multiple HRA. Abnormalities of chromosome 13 were of prognostic significance after adjusting for other prognostic factors.
Cheers!
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Re: New study about impact of chromosomal abnormalities
Here is an earlier thread on this subject from 2015 originally posted by Multibilly.
It had an interesting take on t(14;16) that indicates it may not be high risk.
"Great article - cytogenetics (chromosomal abnormalities)" (Nov 3, 2015)
It had an interesting take on t(14;16) that indicates it may not be high risk.
"Great article - cytogenetics (chromosomal abnormalities)" (Nov 3, 2015)
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: New study about impact of chromosomal abnormalities
Hi Ron,
Thanks for pointing out Multibilly's forum post about that excellent article. When I was writing the post above that starts this thread, I thought about mentioning Multibilly's post. I decided not to so that my post would not be too long.
For those who are interested in the t(14;16) topic, the controversy about whether or not it is truly a marker of high-risk disease has to do with the fact that patients with t(14;16) are much more likely to have kidney damage at diagnosis. So the effect on survival that is seen when patients have t(14;16) may not be due to the disease being more aggressive. Instead, it may be due to the kidney damage that often comes with t(14;16) disease. In fact, one study looked at the impact of t(14;16) disease on prognosis, controlling for the presence of kidney disease, and found that outcomes for t(14;16) patients who did not have kidney damage at diagnosis were similar to those of standard risk patients.
Thanks for pointing out Multibilly's forum post about that excellent article. When I was writing the post above that starts this thread, I thought about mentioning Multibilly's post. I decided not to so that my post would not be too long.
For those who are interested in the t(14;16) topic, the controversy about whether or not it is truly a marker of high-risk disease has to do with the fact that patients with t(14;16) are much more likely to have kidney damage at diagnosis. So the effect on survival that is seen when patients have t(14;16) may not be due to the disease being more aggressive. Instead, it may be due to the kidney damage that often comes with t(14;16) disease. In fact, one study looked at the impact of t(14;16) disease on prognosis, controlling for the presence of kidney disease, and found that outcomes for t(14;16) patients who did not have kidney damage at diagnosis were similar to those of standard risk patients.
Re: New study about impact of chromosomal abnormalities
Do you think this will have an impact on the IMWG's classifications of risk? I have t(4;14), which they classify as intermediate, but Mayo classifies as high, but I also have monosomy 13. So will that combination now be taken into consideration since this is the first large study to address that?
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Scott C - Name: Scott C
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: 6/17
- Age at diagnosis: 52
Re: New study about impact of chromosomal abnormalities
Hi Scott,
As I understand it, t(4;14) is already considered a high-risk marker by the IMWG. See:
Sonneveld, P, et al, "Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group," Blood, March 2016 (full text of article)
Relevant text:
"Translocations t(4;14), t(14;16), t(14;20), and del(17/17p) and any nonhyperdiploid karyotype are HR cytogenetics in NDMM regardless of treatment."
As I understand it, t(4;14) is already considered a high-risk marker by the IMWG. See:
Sonneveld, P, et al, "Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group," Blood, March 2016 (full text of article)
Relevant text:
"Translocations t(4;14), t(14;16), t(14;20), and del(17/17p) and any nonhyperdiploid karyotype are HR cytogenetics in NDMM regardless of treatment."
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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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