The Lancet Haematology, Volume 1, Issue 1, Pages e28 - e36, October 2014
This article can be found in the following
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Copyright © 2014 Elsevier Ltd All rights reserved.
Clinical course of light-chain smouldering multiple myeloma (idiopathic Bence Jones proteinuria): a retrospective cohort study
Prof Robert A Kyle MD a 
,
, Summary
Background
Bence Jones proteinuria is a disorder that is
defined by the excretion of monoclonal light-chain protein. About 15—20% of
patients with multiple myeloma secrete monoclonal light chains only, without
expression of the normal immunoglobulin heavy chain, which constitutes
light-chain multiple myeloma. The definition, prevalence, and progression of
these premalignant phases of light-chain multiple myeloma have not been fully
characterised. We aimed to identify a subset of patients with idiopathic Bence
Jones proteinuria who had a high risk of progression to light-chain multiple
myeloma analogous to that seen in patients with smouldering multiple
myeloma.
Methods
In this retrospective cohort study, we studied
all patients seen at the Mayo Clinic (Rochester, MN, USA) within 30 days of
diagnosis of idiopathic Bence Jones proteinuria between Jan 1, 1960, and June
30, 2004. Inclusion criteria were monoclonal light chain in the urine (≥0·2 g/24
h), absence of intact monoclonal immunoglobulin (M protein) in the serum, and no
evidence of multiple myeloma, light-chain amyloidosis, or other related
plasma-cell proliferative disorders. The primary endpoint was progression to
symptomatic multiple myeloma or light-chain amyloidosis. We examined the
cumulative probability of progression and the association of potential risk
factors on progression rates to identify patients with a high risk of
progression to multiple myeloma or light-chain amyloidosis.
Findings
We identified 101 patients with idiopathic Bence
Jones proteinuria. During 901 total person-years of follow-up, 27 (27%) patients
developed multiple myeloma and seven (7%) developed light-chain amyloidosis. The
major risk factors for progression were amount of urinary excretion of M protein
per 24 h, proportion of bone marrow plasma cells, presence of a markedly
abnormal free-light-chain ratio (<0 or="">100), and reduction of all
three uninvolved immunoglobulins. Based on the risk of progression, monoclonal
light-chain excretion of 0·5 g/24 h or greater or at least 10% bone marrow
plasma cells, or both, in the absence of end-organ damage was used to define
light-chain smouldering multiple myeloma. The cumulative probability of
progression to active multiple myeloma or light-chain amyloidosis in patients
with light-chain smouldering multiple myeloma was 27·8% (95% CI 14·2—39·2) at 5
years, 44·6% (27·9—57·4) at 10 years, and 56·5% (36·3—70·2) at 15
years.
Interpretation
Light-chain smouldering multiple myeloma as
defined in this study is associated with a high risk of progression to
symptomatic light-chain multiple myeloma, and this subset of patients needs
careful observation and could benefit from clinical trials of early
intervention.
Funding
Jabbs Foundation (Birmingham, UK), US National
Cancer Institute, and Henry J Predolin Foundation (Madison, WI,
USA).
