Hi everyone,
There is a new study by researchers in the Czech Republic that looks at risk factors for progression from MGUS to blood cancers such as multiple myeloma. The study is based on a large sample of people with MGUS (almost 1900 cases), and uses data from 2007 to 2013.
The risk factors for progression that the authors identify are:
1. Serum M-spike of 1.5 g/dL or greater
2. Abnormal kappa-lambda serum free light chain ratio (< 0.26 or >1.65) ratio
3. Bone marrow plasma cell percentage greater than 5%,
4. Immunoparesis (one or more immunoglobulin levels below normal)
5. Age greater than 68
6. Hemoglobin level less than 12.0 g/dL
The authors developed a model of the risk of progression within 10 years of diagnosis based on how many of the above risk factors an MGUS patient has at diagnosis. The risk of progression based on the number of risk factors was as follows:
0 risk factors - 1.6% risk of progression within 10 years;
1 risk factors - 16.9% risk of progression within 10 years;
2 risk factors - 22.9% risk of progression within 10 years;
3 risk factors - 39.4% risk of progression within 10 years;
4-5 risk factors - 52.3% risk of progression within 10 years;
This model is similar to a simpler model developed by the Mayo Clinic, which has only these three risk factors:
1. Non-IgG isotype
2. Serum M-spike greater than 1.5 g/dL
3. Abnormal kappa-lambda serum free light chain ratio
With the following estimated risk of progression with 20 (not 10) years of diagnosis:
0 risk factors - 5% risk of progression within 20 years;
1 risk factors - 21% risk of progression within 20 years;.
2 risk factors - 37% risk of progression within 20 years;
3 risk factors - 58% risk of progression within 20 years.
Here's the reference for the new Czech study:
"A first czech analysis of 1887 cases with monoclonal gammopathy of undetermined significance"
http://onlinelibrary.wiley.com/doi/10.1111/ejh.12894/abstract
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Re: Risk of progression with MGUS - new Czech study
Thanks for posting this, Cheryl.
I attempted to access the full article, but it appears that may require a subscription. I am wondering if having a non-IgG isotope was not considered a risk factor in those arrived at by the Czech study, or should that be considered in addition to the new risk factors you summarized?
I attempted to access the full article, but it appears that may require a subscription. I am wondering if having a non-IgG isotope was not considered a risk factor in those arrived at by the Czech study, or should that be considered in addition to the new risk factors you summarized?
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kap12 - Name: Kristine
- Who do you know with myeloma?: Myself (IgA MGUS)
- When were you/they diagnosed?: September 2016
Re: Risk of progression with MGUS - new Czech study
Thank you very very much, this was very helpful.
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Mojbahar - Name: M
- Who do you know with myeloma?: Self mgus
- When were you/they diagnosed?: Jully 2016
- Age at diagnosis: 48
Re: Risk of progression with MGUS - new Czech study
Hi Kristine,
I also don't have access to the full text of the article. However, it looks like the article is based on a poster that was presented at the American Society of Hematology meeting in 2014. I've included the abstract for that presentation, and a copy of the poster that I found on the Internet, below.
As best I can tell, in the Czech model, it doesn't seem to matter whether or not an MGUS patient has IgG monoclonal protein. This is somewhat similar to what has been found in multiple myeloma in regard to having an IgA M-spike. It used to be thought that having an IgA M-spike meant a myeloma patient's disease was more likely to be aggressive. Nowadays, however, the thinking is that it doesn't matter as much whether or not a myeloma patient has an IgG or IgA M-spike; it's more important what chromosomal abnormalities they have.
In any case, here's the ASH 2014 abstract about the Czech MGUS study:
"Evaluation of Current Clinical Models for Risk of Progression from Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma or Related Malignancies in 2028 Persons Followed in the Czech Republic" (link to abstract)
Authors: Viera Sandecka, Zdenek Adam, Ivan Spicka, Vlastimil Scudla, Evzen Gregora, Vladimir Maisnar, Lucie Brozova, Jiri Jarkovsky, Lucie Rihova, Aneta Mikulasova, David Starostka, Lenka Walterova, Dagmar Adamova, Petr Kessler, Martin Brejcha, Ivan Vonke, Jarmila Obernauerova, Kamila Valentova, Ludek Pour, Jiri Minarik, Jan Straub, Jakub Radocha, Jaromir Gumulec and Roman Hajek
Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is a non-malignant condition associated with a risk of progression to multiple myeloma (multiple myeloma) or related disorders. There are currently 2 clinical models predicting progression from MGUS to multiple myeloma. The Mayo Clinic model uses levels and type of serum monoclonal protein (M-protein) and serum free light chain ratio (sFLC). The Spanish PETHEMA model uses flow cytometry of bone marrow plasmocytes (BMPC) and the presence of DNA aneuploidy.
Purpose: The primary end point was to estimate the cumulative risk of hematologic disorders occurring during the follow-up of our cohort. The secondary end points were: to validate known clinical models suggested by the Mayo Clinic group and the Spanish PETHEMA group for the risk of progression from MGUS to multiple myeloma or related malignancies and to establish a new risk model by the Czech Myeloma Group (CMG model) with better prediction of low-risk MGUS group.
Group: Data for this study were obtained from the Registry of Monoclonal Gammopathies (RMG) acquired from hematologic centers of the Czech Republic. MGUS diagnosis was made according to IMWG criteria. In total, 2028 persons with MGUS were enrolled in the RMG study from May 2007 to June 2013. A total of 93% (1887/2028) of persons were evaluated.
Results: 1887 MGUS persons were followed with median 4 years. Malignancies developed in 8.6% (162/1887) cases; multiple myeloma occurred in 77.2% (125/162) of persons. The risk of progression was 1.5% at 1 year, 7.6% at 5 years and 16.5% at 10 years after diagnosis. The key predictors factors of progression were as follows: age ≥ 69 years, serum M- protein concentration ≥ 1.5 g/dL, BMPC > 5%, pathological sFLC ratio (< 0.26 or >1.65), immunoparesis of polyclonal immunoglobulins, levels of serum hemoglobin at baseline < 12.0 g/dL and the presence of normal plasma cells (nPC) in bone marrow ≤ 5 % identified by multiparametric flow cytometry techniques. Distribution of MGUS persons according to risk groups based on the Mayo Clinic model confirmed predictive power of Mayo Clinic model based on our data although isotype of M- protein was not found as independent predictor. At 10 years, no-risk group had 4.9% risk of progression compared to 16.3%, 24.6%, and 54.9% in groups with 1, 2 or 3 risk factors, respectively (p< 0.001). MGUS group with 1, 2 and 3 risk factors in comparison to the reference group without any risk factor had HR( 2.59 [95% CI: 1.39- 4.84]; p= 0.003, HR 4.79 [95% CI: 2.56-8.93]; p< 0.001, HR 12.97 [95% CI: 5.52-30.48];p< 0.001), retrospectively. Immunoparesis instead of DNA aneuploidy was used together with the presence of abnormal plasma cells (aPCs) to validate the modified PETHEMA model. The rates of progression at 3 years were 2.5%, 8.1% and 28.0% for groups with neither, one or both risk factors, respectively (p< 0.001). MGUS group with 1 and 2 risk factors in comparison to the reference group without any risk factor had HR (3.98 [95% CI: 1.60-9.91]; p= 0.003, HR 14.23 [95% CI: 2.86-70.76]; p< 0.001), retrospectively. Based on the 5 parameters with independent predictive value in the univariate analysis (immunoparesis, serum M-protein quantity ≥ 1.5 g/dL, BMPC > 5%, abnormal sFLC ratio and serum level of hemoglobin < 12.0 g/dL) we proposed a new CMG model. The created CMG model clearly detected MGUS persons at low risk 86.6% (828/956) with the risk of progression 5.6% at 5 years better than previously described models. As expected, the number of MGUS persons with the highest risk of progression was limited to 3.7% only (35/956), with the risk of progression 31.9% at 5 years. The MGUS group with 5 risk factors had 63 times higher hazard of progression compared to reference MGUS group (HR 63.17 [95% CI: 13.99-285.36]; p< 0.001).
Conclusion: In the large cohort of MGUS persons, we confirmed validity of previously considered clinical models for the risk of progression from MGUS to multiple myeloma by the Mayo Clinic group and the Spanish PETHEMA group (model used for SMM). New CMG model for the risk of progression from MGUS to multiple myeloma or related malignancies was established with an advantage for better identification of MGUS persons at low risk (87% of persons with risk of progression below 10% in 5 years) as well as few persons at the highest risk of progression. As a consequence, limited evaluation and visits can be planned in majority of MGUS persons in follow-up.
Here is a PDF file with the poster presentation for the abstract:
I also don't have access to the full text of the article. However, it looks like the article is based on a poster that was presented at the American Society of Hematology meeting in 2014. I've included the abstract for that presentation, and a copy of the poster that I found on the Internet, below.
As best I can tell, in the Czech model, it doesn't seem to matter whether or not an MGUS patient has IgG monoclonal protein. This is somewhat similar to what has been found in multiple myeloma in regard to having an IgA M-spike. It used to be thought that having an IgA M-spike meant a myeloma patient's disease was more likely to be aggressive. Nowadays, however, the thinking is that it doesn't matter as much whether or not a myeloma patient has an IgG or IgA M-spike; it's more important what chromosomal abnormalities they have.
In any case, here's the ASH 2014 abstract about the Czech MGUS study:
"Evaluation of Current Clinical Models for Risk of Progression from Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma or Related Malignancies in 2028 Persons Followed in the Czech Republic" (link to abstract)
Authors: Viera Sandecka, Zdenek Adam, Ivan Spicka, Vlastimil Scudla, Evzen Gregora, Vladimir Maisnar, Lucie Brozova, Jiri Jarkovsky, Lucie Rihova, Aneta Mikulasova, David Starostka, Lenka Walterova, Dagmar Adamova, Petr Kessler, Martin Brejcha, Ivan Vonke, Jarmila Obernauerova, Kamila Valentova, Ludek Pour, Jiri Minarik, Jan Straub, Jakub Radocha, Jaromir Gumulec and Roman Hajek
Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is a non-malignant condition associated with a risk of progression to multiple myeloma (multiple myeloma) or related disorders. There are currently 2 clinical models predicting progression from MGUS to multiple myeloma. The Mayo Clinic model uses levels and type of serum monoclonal protein (M-protein) and serum free light chain ratio (sFLC). The Spanish PETHEMA model uses flow cytometry of bone marrow plasmocytes (BMPC) and the presence of DNA aneuploidy.
Purpose: The primary end point was to estimate the cumulative risk of hematologic disorders occurring during the follow-up of our cohort. The secondary end points were: to validate known clinical models suggested by the Mayo Clinic group and the Spanish PETHEMA group for the risk of progression from MGUS to multiple myeloma or related malignancies and to establish a new risk model by the Czech Myeloma Group (CMG model) with better prediction of low-risk MGUS group.
Group: Data for this study were obtained from the Registry of Monoclonal Gammopathies (RMG) acquired from hematologic centers of the Czech Republic. MGUS diagnosis was made according to IMWG criteria. In total, 2028 persons with MGUS were enrolled in the RMG study from May 2007 to June 2013. A total of 93% (1887/2028) of persons were evaluated.
Results: 1887 MGUS persons were followed with median 4 years. Malignancies developed in 8.6% (162/1887) cases; multiple myeloma occurred in 77.2% (125/162) of persons. The risk of progression was 1.5% at 1 year, 7.6% at 5 years and 16.5% at 10 years after diagnosis. The key predictors factors of progression were as follows: age ≥ 69 years, serum M- protein concentration ≥ 1.5 g/dL, BMPC > 5%, pathological sFLC ratio (< 0.26 or >1.65), immunoparesis of polyclonal immunoglobulins, levels of serum hemoglobin at baseline < 12.0 g/dL and the presence of normal plasma cells (nPC) in bone marrow ≤ 5 % identified by multiparametric flow cytometry techniques. Distribution of MGUS persons according to risk groups based on the Mayo Clinic model confirmed predictive power of Mayo Clinic model based on our data although isotype of M- protein was not found as independent predictor. At 10 years, no-risk group had 4.9% risk of progression compared to 16.3%, 24.6%, and 54.9% in groups with 1, 2 or 3 risk factors, respectively (p< 0.001). MGUS group with 1, 2 and 3 risk factors in comparison to the reference group without any risk factor had HR( 2.59 [95% CI: 1.39- 4.84]; p= 0.003, HR 4.79 [95% CI: 2.56-8.93]; p< 0.001, HR 12.97 [95% CI: 5.52-30.48];p< 0.001), retrospectively. Immunoparesis instead of DNA aneuploidy was used together with the presence of abnormal plasma cells (aPCs) to validate the modified PETHEMA model. The rates of progression at 3 years were 2.5%, 8.1% and 28.0% for groups with neither, one or both risk factors, respectively (p< 0.001). MGUS group with 1 and 2 risk factors in comparison to the reference group without any risk factor had HR (3.98 [95% CI: 1.60-9.91]; p= 0.003, HR 14.23 [95% CI: 2.86-70.76]; p< 0.001), retrospectively. Based on the 5 parameters with independent predictive value in the univariate analysis (immunoparesis, serum M-protein quantity ≥ 1.5 g/dL, BMPC > 5%, abnormal sFLC ratio and serum level of hemoglobin < 12.0 g/dL) we proposed a new CMG model. The created CMG model clearly detected MGUS persons at low risk 86.6% (828/956) with the risk of progression 5.6% at 5 years better than previously described models. As expected, the number of MGUS persons with the highest risk of progression was limited to 3.7% only (35/956), with the risk of progression 31.9% at 5 years. The MGUS group with 5 risk factors had 63 times higher hazard of progression compared to reference MGUS group (HR 63.17 [95% CI: 13.99-285.36]; p< 0.001).
Conclusion: In the large cohort of MGUS persons, we confirmed validity of previously considered clinical models for the risk of progression from MGUS to multiple myeloma by the Mayo Clinic group and the Spanish PETHEMA group (model used for SMM). New CMG model for the risk of progression from MGUS to multiple myeloma or related malignancies was established with an advantage for better identification of MGUS persons at low risk (87% of persons with risk of progression below 10% in 5 years) as well as few persons at the highest risk of progression. As a consequence, limited evaluation and visits can be planned in majority of MGUS persons in follow-up.
Here is a PDF file with the poster presentation for the abstract:
ash2014abstract3376.pdf- (1.36 MiB) Downloaded 1982 times
Re: Risk of progression with MGUS - new Czech study
Cheryl,
Thank you for your very detailed follow-up, though I would not say it appears as really good news. The Czech system would give me an increased number of risk factors over half the amount of time. I intend to put this information to immediate use, as it may be helpful in my ongoing effort to pry lab results out of an extremely resistant hematologist! I just recently had my six month lab tests done and have already made two requests to see my complete test results.
Again, thank you for sharing this!
Kristine
Thank you for your very detailed follow-up, though I would not say it appears as really good news. The Czech system would give me an increased number of risk factors over half the amount of time. I intend to put this information to immediate use, as it may be helpful in my ongoing effort to pry lab results out of an extremely resistant hematologist! I just recently had my six month lab tests done and have already made two requests to see my complete test results.
Again, thank you for sharing this!
Kristine
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kap12 - Name: Kristine
- Who do you know with myeloma?: Myself (IgA MGUS)
- When were you/they diagnosed?: September 2016
Re: Risk of progression with MGUS - new Czech study
Studies like this have a lot of merit, but I also urge people to speak with their doctor about the specifics of their case. According to previous studies, I was pretty high risk of progression, but my doctor did the calculations using my blood tests and bone marrow biopsy results. There are certain chromosomal markers they look for, and this factors into progression risk. I ended up being much lower risk of progression than I originally thought.
It's still a guessing game, and nobody really knows yet why some people progress and others don't. I'm hoping the more we learn about MGUS / multiple myeloma, the better the treatments and maybe one day even prevention.
It's still a guessing game, and nobody really knows yet why some people progress and others don't. I'm hoping the more we learn about MGUS / multiple myeloma, the better the treatments and maybe one day even prevention.
Re: Risk of progression with MGUS - new Czech study
Very interesting information. I just read the Mayo Clinic study, so this intrigued me as well.
Thanks for sharing.
swmorgan
Thanks for sharing.
swmorgan
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swmorgan - Name: Shan
- When were you/they diagnosed?: August 2016 IgM MGUS
- Age at diagnosis: 54
Re: Risk of progression with MGUS - new Czech study
Very interesting study. My haematologist had a look at it and could not figure out why they excluded the type of MGUS from the risk factors. He did, however, promise me to have a more detailed look at it as it appears to be a credible study.
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Aussie - Name: Assue
- Who do you know with myeloma?: Nil
- When were you/they diagnosed?: 2015
- Age at diagnosis: 37
Re: Risk of progression with MGUS - new Czech study
A couple of things in regard to this study that may address some of the questions or concerns people have posted above.
First, this study was published in a respected, peer-reviewed medical journal (the European Journal of Haematology), using data from almost 1900 MGUS patients. Also, the Czech myeloma group is well regarded in multiple myeloma research circles.
Second, the researchers did in fact investigate whether the type of a patient's MGUS (IgG or not IgG) affects their risk of progression. If you look at the PDF for the ASH abstract, which I included with one of my posts above, you'll see in Figure 2 in the PDF that the researchers checked whether a patient's IgG type had any statistically significant correlation with their risk of progression. The relevant results are in the row of the figure labeled "Type of paraprotein", and there are two options: "normal" and "abnormal (non IgG)". 8.3% of the "normal" (IgG) patients progressed, and 9.1% of the "abnormal" non-IgG patients progressed. The researchers determined that this 0.8% difference in risk of progression was not statistically significant, and you can see why by looking at differences in risk of progression in some of the other rows in Figure 2.
I don't want to claim that this study is the be-all and end-all of MGUS risk-of-progression studies. But it certainly provides a lot richer detail than the standard Mayo model that so many people quote.
First, this study was published in a respected, peer-reviewed medical journal (the European Journal of Haematology), using data from almost 1900 MGUS patients. Also, the Czech myeloma group is well regarded in multiple myeloma research circles.
Second, the researchers did in fact investigate whether the type of a patient's MGUS (IgG or not IgG) affects their risk of progression. If you look at the PDF for the ASH abstract, which I included with one of my posts above, you'll see in Figure 2 in the PDF that the researchers checked whether a patient's IgG type had any statistically significant correlation with their risk of progression. The relevant results are in the row of the figure labeled "Type of paraprotein", and there are two options: "normal" and "abnormal (non IgG)". 8.3% of the "normal" (IgG) patients progressed, and 9.1% of the "abnormal" non-IgG patients progressed. The researchers determined that this 0.8% difference in risk of progression was not statistically significant, and you can see why by looking at differences in risk of progression in some of the other rows in Figure 2.
I don't want to claim that this study is the be-all and end-all of MGUS risk-of-progression studies. But it certainly provides a lot richer detail than the standard Mayo model that so many people quote.
Re: Risk of progression with MGUS - new Czech study
Thanks for the update. Hopefully it's not saying anything bad about my doctor, but he also told me it's an interesting piece. Just wondering why it's not getting more attention.
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Aussie - Name: Assue
- Who do you know with myeloma?: Nil
- When were you/they diagnosed?: 2015
- Age at diagnosis: 37
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