Prediction of Response and Progression in Multiple Myeloma with Serum-free Light Chains
(sFLC): Corroboration of the International Myeloma Working Group (IMWG) Criteria
R. Khoriaty a, M. A. Hussein b, J. Lally a, M. Kelly a, M. Kalaycio a, R. Baz a
Cleveland Clinic Taussig Cancer Center a and H. Lee Moffitt Cancer and Research Institute b
Background
Response Definitions
Results
The serum free light (sFLC) assay
The median age of the 89 identified patients was 61 years (range 41-87) and 58 patients (65%) were males The involved light chain was
Complete
Disappearance of all evidence of serum
was proposed as a tool for the
kappa in 67 pts (75%). Table 3 summarizes the patients demographics and baseline laboratory evaluations. By EBMT criteria, 4
Remission
and urine M-components on
assessment
of
response
in
patients had a complete remission, 22 patients had a partial remission, 34 patients had stable disease, 26 patients had progressive
(CR)
electrophoresis as well as by
patients with non-secretory or
disease and 3 were inevaluable (table 4). Only 43 of the 89 pts (48%) had an involved FLC 10mg/dL; of which 14 had a PR, 8 had SD,
immunofixation studies.
oligosecretory MM and patients
18 had PD, and 3 were inevaluable. Table 5 reviews the test characteristics for sFLC assay for the prediction of response or
with
primary
amyloidosis.
Partial
A greater than 50% reduction in the
progression.
Response and progression criteri
Remission
serum paraprotein, and if present, a
ia
N=89
Sensitivity
Specificity
PPV
NPV
have
been
proposed
by
the
(PR)
greater than 90% reduction in the urine
International
Myeloma
Working
light chain excretion.
Age (years),
Response
81% (51-94%)
83% (65-92%)
64% (38-83%)
92% (68-98%)
Group (IMWG), but have not been
Median (range)
61 (41-87)
Stable disease A stable serum and urine paraprotein
Progression
93% (68-98%)
80% (62-91%)
72% (49-87%)
95% (78-99%)
thoroughly validated.
(SD)
(within 25%).
Gender,
Table 5. Test characteristics of the sFLC assay. PPV/NPV: positive/negative predictive value
Progressive
25% increase in serum paraprotein or
Patients and Methods
% Males
65%
disease (PD)
plasmacytoma
N=89
Conclusions
Electronic records of patients with
Table 1. Response definition by the EBMT criteria
Heavy chain, %
Involved sFLC>10mg/dL, N
43 (48%)
The sFLC reliably predicts response
multiple
myeloma
enrolled
in
IgG
67%
(%)
various
clinical
trials
at
the
and progression in MM. However,
Partial Remission 50% or greater decrease in the
IgA
24%
sFLC response, N (%)
Cleveland Clinic Taussig Cancer
half the pts had an involved sFLC
(PR)
difference of the involved and
PR
14 (32%)
Center
between
4/2004
and
that
would
not
be
considered
Light chain,
uninvolved free light chain.
SD
8 (19%)
12/2006 were reviewed. Response
evaluable by IMWG criteria, which
% Kappa
75%
PD
18 (42%)
to treatment and progression were
Stable Disease
Less than 50% decrease and less
limits its potential use.
Not evaluable
3 (7%)
assessed
using
the
European
(SD)
than 25% increase in the difference
Baseline 2 microglobulin,
Blood
and
Bone
Marrow
between the involved and uninvolved
mg/dL
3.6 (1.4-
EBMT response, N (%)
References
Tr
T ansplantation
(EBMT)
criteria
serum free light chain
criteria
Median, (range)
47.7)
CR
4 (5%)
()
(table 1) and the sFLC criteria (in
PR
22 (25%)
Progressive
Greater than 25% increase in the
1- Durie B et al.. Leukemia 2006;
patients with evaluable involved
Baseline creatinine, mg/dL
SD
34 (38%)
disease (PD)
difference between the involved and
20(9): 1467-73.
sFLC; iFLC 10 mg/dl (100mg/l)).
uninvolved serum free light chain
Median, (range)
1.1 (0.6-
PD
26 (29%)
sFLC
responses
were
defined
7.7)
Not evaluable
3 (3%)
2- Blade J et al. British Journal of
using the IMWG criteria (table 2).
Haematology 1998;102:1115-23.
Table 2. Response definition using the sFLC criteria of
Table 3. Patients characteristics at
Table 4.Classification of responses according to
IMWG
baseline
the EBMT and sFLC criteria