Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance.
We hypothesized that the presence of monoclonal free kappa or lambda immunoglobulin light chains in monoclonal gammopathy of undetermined significance (MGUS), as detected by the serum free light chain (FLC) assay increases the risk of progression to malignancy. Of 1384 patients with MGUS from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 1148. At a median follow-up of 15 years, malignant progression had occurred in 87 (7.6%) patients. An abnormal FLC ratio (kappa-lambda ratio < 0.26 or > 1.65) was detected in 379 (33%) patients. The risk of progression in patients with an abnormal FLC ratio was significantly higher compared with patients with a normal ratio (hazard ratio, 3.5; 95% confidence interval [CI], 2.3-5.5; P < .001) and was independent of the size and type of the serum monoclonal (M) protein. Patients with an abnormal serum FLC ratio, non-immunoglobulin G (non-IgG) MGUS, and a high serum M protein level (> or = 15 g/L) had a risk of progression at 20 years of 58% (high-risk MGUS) versus 37% with any 2 of these risk factors (high-intermediate risk), 21% with one risk factor (low-intermediate risk), and 5% when none of the risk factors were present (low risk).
Rajkumar
S Vincent
SV
Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Kyle
Robert A
RA
Therneau
Terry M
TM
Melton
L Joseph
LJ
Bradwell
Arthur R
AR
Clark
Raynell J
RJ
Larson
Dirk R
DR
Plevak
Matthew F
MF
Dispenzieri
Angela
A
Katzmann
Jerry A
JA
D000368:Aged; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D011237:Predictive Value of Tests; D012307:Risk Factors
D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains