LES GAMMAPATHIES

MONOCLONALES

2023 - 2024 Gammapathies Monoclonales 1

 ELECTROPHORESE DES PROTIDES

Gammapathies Monoclonales 2 2023 - 2024

 PIC GAMMA A BASE LARGE: GAMMAPATHIE POLYCLONALE
= Sd INFLAMMATOIRE

Gammapathies Monoclonales 3 2023 - 2024

 ELECTROPHORESE DES PROTIDES

PIC GAMMA
A BASE ETROITE
Gammapathies Monoclonales 4 2023 - 2024
 1. IMMUNOFIXATION
2. DIAGNOSTIC ETIOLOGIQUE
3. SUIVI

Gammapathies Monoclonales 5 2023 - 2024

 IMMUNOFIXATION

Gammapathies Monoclonales 6 2023 - 2024

 Gammapathies monoclonales
Définition IMMUNOFIXATION

• Ig Monoclonale secrétée par un clone plasmocytaire ou

lymphoplasmocytaire
• Ig complète ou chaines légères libres
• N’est pas synonyme de malignité
• Myélome et états associés
Gammapathie monoclonale Ig G lam
• Sd Lymphoprolifératifs
• Pathologies non malignes
• Situations fréquentes: 1% de la population
• Démarche diagnostique et de suivi

Gammapathies Monoclonales 7 2023 - 2024

 Gammapathies monoclonales
Incidence
20,00% 19,20%

18,00%
16,00% 1% de la population générale
3% de la population > 50 ans
14,00%
12,00%
10,00%
8,00% 6,70%
6,00%
3,70%
4,00% 2,60%
2,00% 0,50%
0,00%
< 60 ans 60 - 70 ans 70 - 80 ans 80 - 90 ans > 90 ans
Gammapathies Monoclonales 8 2023 - 2024
 Gammapathies monoclonales
Incidence
856 patients avec gammapathies monoclonales
3%
5%
15%

IgG
12%
IgM
56% IgA
Biclonale
Chaines légères

Gammapathies Monoclonales 9 2023 - 2024

Kyle RA, Hematol Oncol Clin North Am, 1992: 347 - 58
 Gammapathies monoclonales
Diagnostic
856 patients avec gammapathies monoclonales
2%
4% 2%
9%
MGUS
5%
3% MM
LLC
12% LNH
63%
Amylose
SMM
Plasmocytome
MW

Gammapathies Monoclonales 10 2023 - 2024

Kyle RA, Hematol Oncol Clin North Am, 1992: 347 - 58
 Gammapathies monoclonales
Etiologies non malignes
* Maladies auto-immunes:
* Sd de Gougerot-Sjogren +++
* LED, PR,
* Pathologies infectieuses: Ig monoclonales transitoires
* EBV, CMV, HVC, HVB
* Toxoplasmose, Paludisme
* Salmonellose, Leptospirose
* Immunodépression
* VIH, Post greffe,
* Congénitale
* Cirrhose, Hépatopathies chroniques
* POEMS syndrome
Gammapathies Monoclonales 11 2023 - 2024
 Gammapathies monoclonales
Etiologies non malignes

* Sd d’hyperperméabilité capillaire
* Dermatose neutrophiliques
* Sd de Schnitzler,
* Xanthomatose,
* Mucinose papuleuse,
* Xanthogranulomatose necrobiotique…

Gammapathies Monoclonales 12 2023 - 2024

 Gammapathies monoclonales
Pathologie Maligne

* Myélome Multiple
* MGUS
* Amylose
* Waldenström
* Sd lymphoprolifératif:
* LLC IgM
* MZL, MCL…

Gammapathies Monoclonales 13 2023 - 2024

Best Practices in the Treatment of Patients With Multiple Myeloma
clinicaloptions.com/oncology

Updated IMWG Criteria for Diagnosis of

Multiple Myeloma
MGUS Smoldering Myeloma Multiple Myeloma
§ M protein < 3 g/dL § M protein ≥ 3 g/dL (serum) § Underlying plasma cell
§ Clonal plasma cells in BM or ≥ 500 mg/24 hrs (urine) proliferative disorder
< 10% § Clonal plasma cells in BM § AND 1 or more myeloma
§ No myeloma defining ≥ 10% to 60% defining events
events § No myeloma defining § ≥ 1 CRAB* feature
events § Clonal plasma cells in BM
≥ 60%
§ Serum free light chain ratio
≥ 100
§ > 1 MRI focal lesion

*C: Calcium elevation (> 11 mg/dL or > 1 mg/dL higher than ULN)
R: Renal insufficiency (creatinine clearance < 40 mL/min or serum creatinine
> 2 mg/dL)
A: Anemia (Hb < 10 g/dL or 2 g/dL < normal)
B: Bone disease (≥ 1 lytic lesions on skeletal radiography, CT, or PET-CT)

Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-e548.

Best Practices in the Treatment of Patients With Multiple Myeloma
clinicaloptions.com/oncology

MGUS

MM
 ples fromsion 229
to study their serum sample.
participants who were They known
were not tolimitthroughout
the number of thediagnostic tests to investi-
data-collection period, from 4.4
included in the prevalence estimate. The median gate the abnormality, because in most cases, the
have MGUS at study entry would have been ana- percent in the first year to 3.2 percent through

Gammapathies monoclonales
age of this group was 65.9 years, and 47.4 percent presence of a small monoclonal protein will be
lyzed. Thus,
were men. 694Sixty-five
of the 21,463 Olmsted
(3.7 percent) Countyunrelated
had MGUS. the last year
to the of sample
patient’s medical collection (P = 0.41). Thus,
problem. In fact,
residentsThe(3.2
medianpercent) had MGUS.
monoclonal immunoglobulin value the patients presence who of suchsought medicalimmuno-
a monoclonal care frequently and,
MGUS waswas0.6 gfound
per deciliter,
in 350 andofthe9469
isotype was IgG
men, in globulin
as com- can be coincidental
therefore, had blood evensamples
among patients
analyzed earlier
Monoclonal
pared with Gammopathy
69.2 percent. These values are similar to of
344 of 11,994 women (3.7 percent vs.example,
the long-time residents of Olmsted County.
thoseUndetermined
for in whom a plasma-cell disorder
wereelderly
at nopatients Significance
greaterinrisk is suspected. For
for MGUS than the appar-
whom systemic amy-
2.9 percent, P<0.001) (Table 3). Of the 20,072loidosis
Epidémiologie entlyis healthier
diagnosed population
may have senile whosystemic
did not seek medi-
Olmsted County residents Dis cuswhose sion race or ethnicamyloidosis cal care andregularly
an unrelated(and
MGUS,hadrather
blood
thansamples ana-
group was known, 97.3 percent were white anda monoclonal lyzed later). protein associated with primary
1.4 § Although the term “monoclonal gammopathy of systemic amyloidosis. Nevertheless, all patients
De were
percent Janvier Asian.1995 Of theà605 Décembre
patients with 2001
undetermined significance,” or “MGUS” was in- with MGUS must be monitored indefinitely for
MGUS whose Laboratory Characteristics
21463race
§ troduced more or ethnic
résidents
than group
25 yearsdeago1Olmsted
andwas known,
long-term county,
progression Minnesota
to a malignant condition.
99.3 percent
studies were white. have been reported,1,2,20
of the prognosis Theprevalence
The isotype of of MGUS
the monoclonal
increases withimmunoglobulin
ad-
§
The weAge
overall >
are unaware50 ans
of any previous
prevalence of MGUS studieswasthat3.2
havepervancing
wasage, IgGbutinafter
68.9adjustment
percentfor ofthetheconcen-
694 patients with
established the prevalence of MGUS in a geo- tration of the monoclonalRAprotein, the annual risk 354:1362-9
100 persons who were 50 years of age or older MGUS, IgM in 17.2
graphically defined population with the use of of progression to myeloma or a related cancer is
percent,
Kyle, IgA
N Engl J Med, in 10.8 percent,
2006,
(95 percent
sensitiveconfidence interval,
laboratory techniques. With3.0 to of
the use 3.5)not and
affectedbiclonal
by age orinthe3.0duration
percent. The 2serum light-
of MGUS.
(Table 3).
ourAge-adjusted
computerized system, rates were higherresults
we obtained in menYoungerchainpatients
type was kappalikely
are more in 62.0 percent
to have pro- and lambda
(4.0 perfrom
100; 76.695percent
percentof theconfidence
enumerated population
interval,of3.5gression
in 37.9 to cancer
percent during their lifetimes
of these simply The mono-
694 patients.
Olmsted County that was 50 years of age or older,
and MGUS was found in 3.2 percent. The preva-
clonal
10
immunoglobulin concentration was less
Table 3. Prevalence of MGUS According to Age Group and Sex among than 1.00 g per deciliter in 63.5 percent Men of pa-
lence of MGUS in this study of Olmsted County
Residents of Olmsted County, Minnesota.
residents is approximately twice that reported in tients,
8 1.00 to 1.49 g per deciliter in 16.6 percent,

Prevalence of MGUS (%)

7,8
Age Men some otherWomen studies (Table 1). In particular,
Total the 1.50 to 1.99 g per deciliter in 15.4 percent, and at
5.3 percent prevalence of MGUS among the Olm-
stednumber/total
County residentsnumber (percent)*
70 years or older was almost
least6 2.00 g per deciliter in 4.5 percent; it was too
Women
50–59 yr 82/4038 (2.0)double that reported
59/4335 (1.4) previously. 7,8
141/8373 (1.7)
low to measure in 91 patients (13.1 percent). Indi-
4
Our results are almost fully representative of vidual values ranged from unmeasurable to 2.94 g
60–69 yr 105/2864 (3.7)the entire 73/3155 (2.3) 178/6019
population and are unlikely to be dif- (3.0)
per2 deciliter; the median was 0.5 g per deciliter,
70–79 yr 104/1858 (5.6)ferent had the total
101/2650 (3.8)population been analyzed.
205/4508 (4.6)
Within the study cohort, the frequency of MGUS or 0.7 g per deciliter if the unmeasurable proteins
≥80 yr 59/709 (8.3)among111/1854
subjects who (6.0) 170/2563
gave permission (6.6)
to perform were 0 excluded. The concentration of uninvolved
50 60
Total the serum
350/9469 (3.7)† studies(2.9)†
344/11,994 was the same as that among
694/21,463 (3.2)†‡ (normal, polyclonal, or 70background) 80
immuno- 90

Gammapathies Monoclonales subjects who did not give permission. The 16 rela- Age (yr) 2023 - 2024
globulins was reduced in 124 of the 447 patients
* The percentage was calculatedtively
as high prevalence
the number of MGUS
of patients withinMGUS
the general
divided Figure 1. Prevalence of MGUS According to Age.
whose immunoglobulin concentration was mea-
Best Practices in the Treatment of Patients With Multiple Myeloma
clinicaloptions.com/oncology

Smoldering Multiple Myeloma

100
Smoldering MM
Probability of Progression (%)

MGUS
80 27% will convert in 15 years
Roughly 2% per year 78
73
66
60
27% more will convert in remaining 15 yrs
51 ~ 2% per yr
40
51% will convert in first 5 yrs
~ 10% per yr
20 21
4 16
10
0
0 5 10 15 20 25
Yrs Since Diagnosis
Kyle RA, et al. N Engl J Med. 2007;356:2582-2590. Greipp PR, et al. J Clin Oncol. 2005;23:3412-3420.
 MGUS: BILANS ET SUIVI
CLINIQUE ET BIOLOGIQUE

* CLINIQUE:
* Recherche de signes suggérant une évolution vers MM:
* Anémie, Fatigue, Douleurs osseuses, Perte de poids…
* BIOLOGIE:
* Gammapathie: sang et urine
* FLC: Free Light Chains
* NFS
* Myélogramme
* Ionogramme
Gammapathies Monoclonales 18 2023 - 2024
 MGUS: TRAITEMENT

* Pas de traitement consensuel

* Pas de traitement permettant de retarder ou prévenir
l’évolution vers un MM

Gammapathies Monoclonales 19 2023 - 2024