Diapositiva 1

Applicazioni della misura delle Free Light Chain
nella pratica clinica
Maria Teresa Petrucci
Serum free light chain immunoassay
Heavy
chain
Kappa
Light
chain
Hidden
surface
Lambda
Exposed
surface
Serum free light chain immunoassay
Heavy
chain
Light
chain
Kappa
Hidden
surface
Lambda
Exposed
surface
Discrasie plasmacellulari
Mieloma Multiplo
Gammopatie monoclonali
Plasmocitoma localizzato
Macroglobulinemia di Waldenstrom
Associate ad altre sindromi linfoproliferative
Crioglobulinemie
Amiloidosi
Forme associate ad altre malattie
Screening for
Monoclonal Gammopathies
• Serum electrophoresis
→ Monoclonal intact immunoglobulins
• Urine electrophoresis
→ Monoclonal free light chains
MM: laboratorio
MM micromolecolare: Bence Jones
Measurement of serum free light chains
Diagnosis
 Prognosis
Management
Light Chain Multiple Myeloma
Normal sera
Kappa LCMM
Lambda LCMM
Renal impairment
(CKD2)
Hutchison, unpublished data; Bradwell, Lancet 2003; 361: 489-491
Intact Immunoglobulin MM
No correlation between Ig’ and sFLC
100000
Serum l FLC (mg/L)
n = 120 IgGl MM patients
10000
1000
100
10
1
0
20
40
60
80
100
Total IgG (g/L)
Mead et al. Br J Haematol 2004;126 : 348 – 54
Light chain concentration (mg/L)
Sensitivity of light chain analysis techniques
1000
SPE
100
CZE
sIFE
10
UPE
Normal range in serum
1
sFLC
uIFE
Recommendations for the use of the serum FLC assay
screening
•serum FLC assay in combination with serum PEL and serum IFE is
sufficient to screen for pathological monoclonal plasmaproliferative
•AL requires all the serum tests as well as the 24-h urine IFE.
•If a diagnosis of a plasma cell disorder is made, a 24-h urine for PEL
and IFE is essential for all patients.
Recommendations for the use of the serum FLC assay
prognosis
The serum FLC assay should be measured
at diagnosis for all patients with
MGUS
smoldering
active multiple myeloma
solitary plasmacytoma
AL amyloidosis
Risk of progression 1% per year
MGUS
?
AL
amyloid
WM
IgM
lymphoma
CLL
Solitary
plasmacytoma
MM
LCDD
Follow up MGUS patients: How frequently?
Monoclonal Gammopathy of Undetermined
Significance (MGUS)
Risk Factors for progression:
• Serum M protein >15g/L
• Serum M protein NOT IgG
Kyle R. NEJM 2002; 346: 564-569
Monoclonal Gammopathy of Undetermined
Significance (MGUS)
Risk Factors for progression:
• Serum M protein >15g/L
• Serum M protein NOT IgG
•sFLC ratio
Kyle R. NEJMRajkumar
2002;
346:
564-569
Blood 2005; 106: 812-817
60
50
(/ = <0.26 or >1.65)
Normal FLC ratio
(/ = 0.26 – 1.65)
10
20
30
40
Abnormal FLC ratio
0
Cumulative probability of progression (%)
MGUS progression
0
5
10
15
20
25
30
Years
Rajkumar Blood 2005; 106: 812-817
MGUS risk stratification model incorporating
M-protein size, type and FLC ratio
Risk of progression
No. of abnormal
risk factors
No. patients
Absolute risk of
progression at
20 years*
Low
0
449
2%
Low-Intermediate
1
420
10%
High-Intermediate
2
226
18%
High
3
53
27%
* Accounting for death as a competing risk
Rajkumar Blood 2005; 106: 812-817
Risk of progression
Overall survival
Recommendations for the use of the serum FLC assay
response assessment
Serial FLC ascertainment should be routinely
performed in patients with:
•AL amyloidosis
•multiple myeloma with oligosecretory disease
It should also be done in all patients who have
achieved a CR to determine whether they have
attained a stringent CR.
Profondità di risposta
Tempo alla Progressione
Inizio del
trattamento
MR
PR
VGPR
nCR
CR
sCR
Tempo
La profondità delle risposte è correlata al TTP
International guidelines for sFLC analysis in
MM and related disorders
• Assessment of response
• All MM patients to define a stringent CR
CR
Stringent CR
Negative S/U IFE
BM plasma cells ≤ 5%
Negative S/U IFE
Normal sFLC ratio
Absence of clonal cells in BM
Dispenzieri et al. Leukemia 2009: 23, 215–224
Durie et al., Leukemia, 2006. 20, 1467-73
Rapid evaluation of response to chemotherapy
Dispenzieri et al.
• Retrospective analysis of ECOG trial E9486
“FLC response after 2 months of
• VBMCP  IFN or  cyclophosphamide
therapy was superior to early
• 399 patients
M-protein measurement to predict
• Assessed sFLC and M-protein responses
overall response.”
to therapy
Dispenzieri et al. Blood 2008; 111: 4908 - 4915
Light chain escape
“Rising monoclonal free light chain production
at relapse without increased monoclonal intact
immunoglobulin”
Drayson et al.
• Myeloma IX trial
• Estimate incidence:
5 % for IgG MM
15 % for IgA MM
Drayson, M.T., et al., Clin Lymphoma Myeloma, 2009. February: 346a.
CONCLUSIONS
Screening: serum FLC assay in combination with serum protein
electrophoresis and immunofixation yields high sensitivity
Prognosis: FLC assay is of major prognostic value in virtually every
plasma cell disorder
Monitoring: FLC assay allows for quantitative monitoring of patients
with oligosecretory plasma cell disorders, including patients with AL
Response evaluation: rFLC a requirement for documenting stringent
complete response according to the International Response Criteria

Download Report