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Multiple Myeloma: diagnosis and prognostic factors
N MeulemanMay 2015
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Diagnosis
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Diagnostic assessment of myeloma:what should we know?
• Is it really a myeloma?
• Is there a need for treatment?
• What is the prognosis of my patient?
• What would be the best treatment for my patient?
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Evaluation of myeloma patient:
Palumbo A et al; J Clin Oncol 2014
SMM
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Is it always so simple?
• 76 years old man
– MP IgGκ: 2.5 gr/dl– BM aspiration: 23% of
plamocytes– Cytogenetic: pending– Créatinine level: 2mg/dl– No anemia or
hypercalcemia– whole body x-ray
• HTA
• Diabetes
• Recent infection
• CRI
Is it a real symptomatic myeloma or a SMM with CRI?
You need to complete the evaluation
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« The CRAB traps »
• Calcium– Hyperparathyroidism
• Renal insufficiency– Frequency of MGUS and
RI increase with age
– Hypertension, diabetes…
– Amyloidosis
– MGRS• Monoclonal gammopathy
of renal significance
• Renal toxicity of small level of MP
• Anaemia
– Iron- B12- folic acid deficency
– Renal insufficiency
• Bone lesions
– Cancer incidence increase with age (prostate, breast..)
– OsteoscleroticlesionPOEMS
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Our patient
• Créatinine level: 1,7mg/dl• 24 hours urine collection
– Proteinuria: 378mg/ alb>
• Β2m : 6,5 mg/l
• Albumine: 3.6 gr/dl
• LDH : 502 > to the normal value
• MRI of the spine and the pelvis– 3 nodulars lesions > 5mm– Diffuse infiltration
• Cytogentics/FISH: – Hyperdypolid status + t(4-14)
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MM: Staging
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Durie-Salmon staging system (1975)
Tumor Load
Our patient: stage IIB
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International Staging System
JCO 2005; 23 : 3412-3420
Classification pronostic ISS
Stade I β2m < 3.5 mg/L
& albumin ≥ 3.5 g/dL
Stade II Not stage I-II
Stade III β2m > 5,5
Patients < 65 y
Patients > 65 y
Our patient: stage III
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ISS
Advantages
• Predict prognosis
• Blood test
• Simple (don’t need specialised lab)
• Reproducible
Limitations
• Established at the begin of new agent area
• Does not detect genetically high-risk patients
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MM: Prognostic factors
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Genetic in MM
BERGSAGEL et al, Blood 2013
Munshi Nc et al. Clin Cancer Res 2011
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Impact of t(4-14) and del 17p
Avet-Loiseau, et al. Blood 2007
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H. Avet Loiseau et al.
Avet-Loiseau H et al., leukemia 2007
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Overall survival according to the number of poor-prognosis factors [ie, age > 55 years; β2-
microglobulin > 5.5 mg/L; t(4;14), del(17p), 1q gains]: zero, one, two, or more than two.
Avet-Loiseau H et al. JCO 2012;30:1949-1952
©2012 by American Society of Clinical Oncology
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P Moreau et al.
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What about the hyperdiploid statusof our patient?
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Role of imaging in the prognosis of MM?
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Role of MRI in the prognosis of MM
• Number of FL:
– > 7 FL in an axial MRI OS
• Diffuse infiltration is associated with:
– High risk cytogenetics
– Poor prognosis
– In SMM a higher risk of progression into symptomatic disease
Walker R, JCO 2007Moulopoulos LA, Am J Hematol. 2012Merz M, Leukemia 2014Hillengass J, JCO 2010
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FDG-PET?
• Sensitivity
– >whole body x-ray
– Comparable of MRI • < diffuse lesions
• > focal lesions
• Detect extra-medullary lesions
• Poor prognosis if >3 FL at diagnosis
• Normalisation of the lesions (ASCT): EFS OS
•Zamagni et al, 2007•Zamagni E, Blood 2011•Bodet-Milin E, 2012
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Renal impairment?
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Does age and comorbidities matter?
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A Simple Score, Based On Geriatric Assessment, Improves Prediction of Survival, and Risk Of
Serious Adverse Events In Elderly NewlyDiagnosed Multiple Myeloma Patients
The higher mortality rate in unfit and frail ptsto higher cumulative incidence of grade ≥3
adverse eventsin particular extra hematologic toxicities
causing subsequent treatmentdiscontinuation.
Larocca et al ASH 2013
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Adaptation des traitements
selon la« fragilité »du patient
Palumbo A et al. Blood 2011;118:4519-4529
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Impact of maximal response
Jl Harrousseau; Blood oct 2009
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Level of CR
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Conclusions
1. Be sure of your diagnosis
2. ISS and cytogenetics remain major prognostic factors
3. New imaging evaluation
4. Assessment of comorbities particularly for elderly patients and - if necessary - adapt the treatment
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Chr 1 abnormalities
Avet-Loiseau H, et al. JCO 2012
Hebraud B, et al. Leukemia 2014
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Avet-Loiseau et al – Leukemia 2012
FISH + ISS model
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Critera of myeloma treatement:The near future
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MM: risk stratification
Patient
• Age
• Ecog performans status
• Comorbidities
• Renal function
Disease
• ISS
• Cytogenetic tests
• LDH
• Renal function
• IgA subtype
• Extra medulary lesions
• GEP, PET, PLI, SFLC
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MM: risk stratification
Patient
• Age
• Ecog performans status
• Comorbidities
• Renal function
Disease
• ISS
• Cytogenetic tests
• LDH
• Renal function
• IgA subtype
• Extra medulary lesions
• GEP, MRI, PET, PLI, SFLC
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Diagnostic criteria:International Myeloma Working Group Consensus
IFM recommendation
Palumbo A et al; J Clin Oncol 2014
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Investigations at diagnosis
• Screening tests
• Tests to establish diagnosis
• Tests for prognosis
• Tests to assess myeloma related organ impairment
History and physical examination!
• Medical history• Elderly: co-morbidities• TE events• Diabetes• Alcohol…
• Physical examination/anamnesis• Signs of neuropathy• Amyloidosis: cardiac,
orthostatic, peripheral oedeme, PNP
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Belgian consensus recommendations
Tablel 3. Examinations at diagnosis
Mandatory Complete blood count, peripheral blood smear, chemistry including calcium and
creatinine, beta-2 microglobulin, LDH, serum protein electrophoresis,
immunofixation, nephelometric quantification of immunoglobulins.
24-hrs urine collection for proteinuria and quantification of Bence Jones proteinuria,
creatinine clearance.
Bone marrow biopsy and aspirate for cytomorphological examination and
immunophenotyping.
Radiological skeletal bone survey (spine, pelvis, skull, chest, humeri, femora).
MRI or computerized tomography (CT) scan of suspected spinal lesions.
Recommended Measurement of serum free light chain levels (sFLC).
Bone marrow conventional cytogenetics and fluorescence in situ hybridisation (FISH)
for t(4;14), t(14;16), del 17p.
Magnetic resonance imaging (MRI) of the total spine.
MRI or computerized tomography (CT) scan of symptomatic bone lesions.
Optional Total skeleton MRI.
Positron emission tomography (PET) scan.
Mandatory = standard; Recommended = for optimal management; Optional = for individual patients
and/or within the context of a clinical study.
albumin
* Recommanded IMMWG 2009 Guidelines for risk stratification in myeloma