Prognostic utility of intact immunoglobulin Ig'κ/Ig'λ ratios in multiple myeloma patients.
To determine whether isotype matched immunoglobulin (Ig; Ig'κ/Ig'λ) ratios had prognostic significance in patients with intact Ig multiple myeloma (MM). Novel immunoassays measuring serum concentrations of the Ig heavy chain/light chain (HLC) subsets IgGκ, IgGλ, IgAκ and IgAλ were compared with monoclonal protein ('M-spike') quantification by serum protein electrophoresis, β(2)-microglobulin (β(2)-M), albumin, serum free light chain (FLC) and cytogenetic markers in relation to outcome in 339 MM patients. Abnormal IgGκ/IgGλ and IgAκ/IgAλ ratios present in the respective tumor isotypes at clinical presentation were predictive of shorter progression-free survival (PFS) (hazard ratio (HR) 1.9; P=0.0002), predominantly due to the suppression of the uninvolved (polyclonal) Ig of the same isotype as the tumor (HR 1.8; P=0.002). No significant associations were observed between PFS and M-spike concentrations, suppression of non-tumor Igs of different isotypes or FLC κ/λ ratios. β(2)-M and HLC ratios were independently prognostic (P=0.045 and P=0.001). A staging system using β(2)-M and extreme HLC ratios (<0.01 or >200) had greater prognostic value than the widely used ISS staging system (HR 1.7; P=0.00002 vs HR 1.3; P=0.017). These results suggest that HLC ratios may have a role in clinical management of MM.
School of Immunity and Infection, University of Birmingham, Birmingham, UK.
A
A
Bradwell
S
S
Harding
N
N
Fourrier
C
C
Mathiot
M
M
Attal
P
P
Moreau
J-L
JL
Harousseau
H
H
Avet-Loiseau
D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood; D007147:Immunoglobulin Light Chains / Q000097:blood; D007145:Immunoglobulin kappa-Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains / Q000097:blood*; D009101:Multiple Myeloma / Q000097:blood* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D015996:Survival Rate; D001613:beta 2-Microglobulin / Q000097:blood
D015415:Biomarkers; D007132:Immunoglobulin Isotypes; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D001613:beta 2-Microglobulin