Multiple Myeloma: diagnosis and prognostic factors

N MeulemanMay 2015

Diagnosis

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?

Evaluation of myeloma patient:

Palumbo A et al; J Clin Oncol 2014

SMM

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

« 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

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)

MM: Staging

Durie-Salmon staging system (1975)

Tumor Load

Our patient: stage IIB

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

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

MM: Prognostic factors

Genetic in MM

BERGSAGEL et al, Blood 2013

Munshi Nc et al. Clin Cancer Res 2011

Impact of t(4-14) and del 17p

Avet-Loiseau, et al. Blood 2007

H. Avet Loiseau et al.

Avet-Loiseau H et al., leukemia 2007

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

P Moreau et al.

What about the hyperdiploid statusof our patient?

Role of imaging in the prognosis of MM?

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

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

Renal impairment?

Does age and comorbidities matter?

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

Adaptation des traitements

selon la« fragilité »du patient

Palumbo A et al. Blood 2011;118:4519-4529

Impact of maximal response

Jl Harrousseau; Blood oct 2009

Level of CR

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

Chr 1 abnormalities

Avet-Loiseau H, et al. JCO 2012

Hebraud B, et al. Leukemia 2014

Avet-Loiseau et al – Leukemia 2012

FISH + ISS model

Critera of myeloma treatement:The near future

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

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

Diagnostic criteria:International Myeloma Working Group Consensus

IFM recommendation

Palumbo A et al; J Clin Oncol 2014

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

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