The study linked below discusses the prognostic impact of suppression of the noninvolved pair of the isotype of the myeloma clone at diagnosis. Although the abstract is short, it contains some interesting conclusions which I don't completely understand. Especially since I am not aware of testing at diagnosis which includes both pairs of the involved isotype.
However, in my non-scientifically trained mind, it does seem to support the positive prognostic impact of secondary MGUS if the secondary MGUS clone is of the same heavy chain as the one involved at diagnosis, especially if the involved heavy chain is, as the abstract concludes, IgG.
In any case, I am interested in others' interpretation of this study and its results.
Reference:
Ludwig, H, et al, "Suppression of the noninvolved pair of the myeloma isotype correlates with poor survival in newly diagnosed and relapsed/refractory patients with myeloma," American Journal of Hematology, Feb 2016 (abstract)
Abstract:
Heavy light chain (HLC) assays allow precise measurement of the monoclonal and of the noninvolved polyclonal immunoglobulins of the same isotype as the M-protein (e.g., monoclonal IgAκ and polyclonal IgAλ in case of an IgAκ myeloma), which was not possible before. The noninvolved polyclonal immunoglobulin is termed 'HLC-matched pair'. We investigated the impact of the suppression of the HLC-matched pair on outcome in 203 patients with multiple myeloma, a phenomenon that likely reflects the host's attempt to control the myeloma clone. Severe (>50%) HLC-matched pair suppression was identified in 54.5% of the 156 newly diagnosed patients and was associated with significantly shorter survival (45.4 vs. 71.9 months, P = 0.019). This correlation was statistically significant in IgG patients (46.4 vs. 105.1 months, P = 0.017), but not in patients with IgA myelomas (32.9 vs. 54.1 months, P = 0.498). At best response, HLC-matched pair suppression improved only in patients with ≥VGPR, indicating partial or complete humoral immune reconstitution during remission in those with excellent response. Severe HLC-matched pair suppression retained its prognostic impact also during follow-up after first response. In the 47 pretreated patients with relapsed/refractory disease, a similar correlation between severe HLC suppression and survival was noted (22.8 vs. not reached, P = 0.028). Suppression of the polyclonal immunoglobulins of the other isotypes than the myeloma protein correlated neither with HLC-matched pair suppression, nor with outcome. Multivariate analysis identified severe HLC-matched pair suppression as independent risk factor for shorter survival, highlighting the impact of isotype specific immune dysregulation on outcome in multiple myeloma.
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Re: Suppression of the noninvolved pair of the myeloma isoty
Hey Andrew,
I happened to see this article earlier today as well. The study discusses the impact of the POLYCLONAL "HLC matched pair: (e.g. the polyclonal IgA-lambda component in somebody that has IgA-kappa myeloma). Keeping strictly with the IgA example and ignoring the other possible heavy / light chain combinations, secondary MGUS would require that both the IgA-lambda and IgA-kappa components be monoclonal, right?
So, it doesn't seem like this article applies to secondary MGUS. It instead seems to reinforce the idea that immunoparesis (the suppression of uninvolved polyclonal immunoglobulins) has a negative prognostic impact, even when it happens to the HLC matched pair (IgA-lambda in this example) that shares the same heavy chain as that found in the original m-spike (IgA-kappa in this example).
At least, that's my take.
I happened to see this article earlier today as well. The study discusses the impact of the POLYCLONAL "HLC matched pair: (e.g. the polyclonal IgA-lambda component in somebody that has IgA-kappa myeloma). Keeping strictly with the IgA example and ignoring the other possible heavy / light chain combinations, secondary MGUS would require that both the IgA-lambda and IgA-kappa components be monoclonal, right?
So, it doesn't seem like this article applies to secondary MGUS. It instead seems to reinforce the idea that immunoparesis (the suppression of uninvolved polyclonal immunoglobulins) has a negative prognostic impact, even when it happens to the HLC matched pair (IgA-lambda in this example) that shares the same heavy chain as that found in the original m-spike (IgA-kappa in this example).
At least, that's my take.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Suppression of noninvolved pair of the myeloma isotype
I must admit that my knowledge is limited. Crudely, my analysis is that monoclonal gammopathies are malignant and polyclonal gammopathies are not. Since the uninvolved pair is polyclonal, it is by definition not malignant, just like the secondary MGUS clone. If the uninvolved pair is suppressed, this is a poor prognostic indicator as suggested in the abstract; the converse being if it is not suppressed, or in the case of secondary MGUS, it becomes dominant, this is a positive prognostic indicator, albeit occurring at different points in the treatment / diagnosis process.
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: Suppression of noninvolved pair of the myeloma isotype
Well, without trying to establish a link between these two different phenomena, the bottom line is that secondary MGUS is generally a good thing and so is having an increased HLC matched pair level.
I wonder if the heavy / light chain assay is going to become more common in the coming years? Today I rarely come across anybody that cites their heavy / light chain test results. I keep meaning to ask my oncologist about ordering the Hevylite assay so that we can see what my various free light chain pair levels are doing as my involved free light chain level slowly improves over time.
I wonder if the heavy / light chain assay is going to become more common in the coming years? Today I rarely come across anybody that cites their heavy / light chain test results. I keep meaning to ask my oncologist about ordering the Hevylite assay so that we can see what my various free light chain pair levels are doing as my involved free light chain level slowly improves over time.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Suppression of noninvolved pair of the myeloma isotype
I didn't think that there was necessarily a link, just a common thread. I have never had the test that would reveal the pair levels either. Just thought that his study might be confirming of the positive prognostic impact of secondary MGUS. From a realistic standpoint, I don't put much actual stock in the whole positive prognostic impact thing, just concentrate on the absence of bad indicators.
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: Suppression of noninvolved pair of the myeloma isotype
Even though it was a little difficult for me to read the abstract, I took some useful things away.
First, it would be very desirable to see if monitoring the assays of the heavy-light chain (HLC) iso-types of people with smoldering multiple myeloma is also prognostic. If so, this might open the door to early treatments smoldering multiple myeloma, and thereby avoid the damages of the active stages of multiple myeloma. This would be a huge step forward. Hallelujah to that!
Second, I also noticed the abstract suggests that the suppression of the HLC-matched pairs may be “a phenomenon that likely reflects the host's attempt to control the myeloma clone.” My hematologist has also remarked about the importance of immune systems in helping suppress clonal expansions. Now I see that there may be evidence that this suppression can cause collateral damage. No free lunch?
Thanks for posting the abstract.
Joe
First, it would be very desirable to see if monitoring the assays of the heavy-light chain (HLC) iso-types of people with smoldering multiple myeloma is also prognostic. If so, this might open the door to early treatments smoldering multiple myeloma, and thereby avoid the damages of the active stages of multiple myeloma. This would be a huge step forward. Hallelujah to that!
Second, I also noticed the abstract suggests that the suppression of the HLC-matched pairs may be “a phenomenon that likely reflects the host's attempt to control the myeloma clone.” My hematologist has also remarked about the importance of immune systems in helping suppress clonal expansions. Now I see that there may be evidence that this suppression can cause collateral damage. No free lunch?
Thanks for posting the abstract.
Joe
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Wobbles - Name: Joe
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: June 2016
- Age at diagnosis: 67
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