Contributions
Abstract: PB2206
Type: Publication Only
Background
Smoldering Myeloma (SMM) is an asymptomatic form of Multiple Myeloma (MM) that might have a course as indolent as monoclonal gammopathy of undetermined significance (MGUS), especially after the first 5 years. Some patients however may insidiously rapidly become symptomatic and as follow-up visits are less frequents in SMM, end organ damage may occur. To avoid such events, three biomarkers (FLCR>100, ≥1 osteolysis and ≥60% plasma cell bone marrow infiltration) were recently established to discriminate asymptomatic MM patients at increased risk of quick evolution, characterizing them, when present, as symptomatic and in need of immediate treatment (ref.1). In spite of the usage of the new IMWG definition criteria, there are still patients evolving relatively early and the actual notion of High risk SMM is quite subjective among scientific groups. The Ig heavy chain can be accurately determined with the Heavy/Light Chain (HLC) ‘Hevylite’ method that measures separately HLC-IgA, -G, -M kappa or lambda, thus allowing exact quantification of the amount of pure monoclonal fraction but also the degree of suppression of uninvolved polyclonal Igs, both being reflected by the corresponding ratios (HLCR). HLCR values in MM (ref.2) and of the uninvolved isotype-specific heavy / light chain (HLC-pair suppression) in MGUS (ref.3) were shown to constitute independent risk factors for progression.
Aims
The aim of this study was to investigate weather involved and uninvolved HLCs values or their ratio can identify accurately SMM patients at risk to progress to symptomatic MM.
Methods
We studied 59 patients with SMM from whom 20 were men and 39 women, with median age 65 (31-84), immunoglobulin type consisted IgG in 51 patients (86,4%) and IgA in 8 patients (13,6%). None of the patients FLCR>100, ≥1 osteolysis or ≥60% plasma cell bone marrow infiltration. Patients were regularly followed (each 3 months) since SMM diagnosis and for a long period (median 98 months). “HevyLite” assay measurements were performed by nephelometry according to the manufacturer’s instructions in frozen sera sample drawn at the time of diagnosis. Statistical analysis was performed by standard methods using the SPSS v24.0. software.
Results
HLCR measurements failed to add prognostic information; the same was true for uninvolved IgG and IgM values. However the summated uninvolved IgA kappa plus IgA lambda (SUAKL) values in IgG SMM and uninvolved isotype-specific IgA alone in IgA patients were significantly prognostic of evolution to MM (p<0,01). Time to evolution was 30,5 months in the 12 patients that progressed; their median SUAKL was 0,95 g/L versus 1,8 g/L in the rest (p<0,01).
Conclusion
SUAKL will probably prove to be useful as a marker of high-risk SMM; its value should indeed be confirmed in a larger series
References :
1.Rajkumar SV, et al.Lancet Oncol. 2014 Nov;15(12):e538-48. doi: 10.1016/S1470-2045(14)70442-5. Epub 2014 Oct 26.
2.Koulieris E, et al.Exp Hematol Oncol. 2012 Apr 23;1(1):9. doi: 10.1186/2162-3619-1-9.
3. Katzmann JA, et al. Leukemia 2012. doi:10.1038/leu.2012.189
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Immunoglobulin, Myeloma, prognosis, Smoldering
Abstract: PB2206
Type: Publication Only
Background
Smoldering Myeloma (SMM) is an asymptomatic form of Multiple Myeloma (MM) that might have a course as indolent as monoclonal gammopathy of undetermined significance (MGUS), especially after the first 5 years. Some patients however may insidiously rapidly become symptomatic and as follow-up visits are less frequents in SMM, end organ damage may occur. To avoid such events, three biomarkers (FLCR>100, ≥1 osteolysis and ≥60% plasma cell bone marrow infiltration) were recently established to discriminate asymptomatic MM patients at increased risk of quick evolution, characterizing them, when present, as symptomatic and in need of immediate treatment (ref.1). In spite of the usage of the new IMWG definition criteria, there are still patients evolving relatively early and the actual notion of High risk SMM is quite subjective among scientific groups. The Ig heavy chain can be accurately determined with the Heavy/Light Chain (HLC) ‘Hevylite’ method that measures separately HLC-IgA, -G, -M kappa or lambda, thus allowing exact quantification of the amount of pure monoclonal fraction but also the degree of suppression of uninvolved polyclonal Igs, both being reflected by the corresponding ratios (HLCR). HLCR values in MM (ref.2) and of the uninvolved isotype-specific heavy / light chain (HLC-pair suppression) in MGUS (ref.3) were shown to constitute independent risk factors for progression.
Aims
The aim of this study was to investigate weather involved and uninvolved HLCs values or their ratio can identify accurately SMM patients at risk to progress to symptomatic MM.
Methods
We studied 59 patients with SMM from whom 20 were men and 39 women, with median age 65 (31-84), immunoglobulin type consisted IgG in 51 patients (86,4%) and IgA in 8 patients (13,6%). None of the patients FLCR>100, ≥1 osteolysis or ≥60% plasma cell bone marrow infiltration. Patients were regularly followed (each 3 months) since SMM diagnosis and for a long period (median 98 months). “HevyLite” assay measurements were performed by nephelometry according to the manufacturer’s instructions in frozen sera sample drawn at the time of diagnosis. Statistical analysis was performed by standard methods using the SPSS v24.0. software.
Results
HLCR measurements failed to add prognostic information; the same was true for uninvolved IgG and IgM values. However the summated uninvolved IgA kappa plus IgA lambda (SUAKL) values in IgG SMM and uninvolved isotype-specific IgA alone in IgA patients were significantly prognostic of evolution to MM (p<0,01). Time to evolution was 30,5 months in the 12 patients that progressed; their median SUAKL was 0,95 g/L versus 1,8 g/L in the rest (p<0,01).
Conclusion
SUAKL will probably prove to be useful as a marker of high-risk SMM; its value should indeed be confirmed in a larger series
References :
1.Rajkumar SV, et al.Lancet Oncol. 2014 Nov;15(12):e538-48. doi: 10.1016/S1470-2045(14)70442-5. Epub 2014 Oct 26.
2.Koulieris E, et al.Exp Hematol Oncol. 2012 Apr 23;1(1):9. doi: 10.1186/2162-3619-1-9.
3. Katzmann JA, et al. Leukemia 2012. doi:10.1038/leu.2012.189
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Immunoglobulin, Myeloma, prognosis, Smoldering