Multiple Myeloma: diagnosis and prognostic factors. N Meuleman May 2015

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1 Multiple Myeloma: diagnosis and prognostic factors N Meuleman May 2015

2 Diagnosis

3 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?

4

5 Evaluation of myeloma patient: SMM Palumbo A et al; J Clin Oncol 2014

6 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

7 «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..) Osteosclerotic lesion POEMS

8 Our patient Créatinine level: 1,7mg/dl 24 hours urine collection Proteinuria: 378mg/ alb> Β 2 m : 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)

9 MM: Staging

10 Durie-Salmon staging system (1975) Tumor Load Our patient: stage IIB

11 International Staging System Patients < 65 y Classification pronostic ISS Stade I Stade II β 2 m < 3.5 mg/l & albumin 3.5 g/dl Not stage I-II Stade III β 2 m > 5,5 Our patient: stage III Patients > 65 y JCO 2005; 23 :

12 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

13 MM: Prognostic factors

14 Genetic in MM BERGSAGEL et al, Blood 2013 Munshi Nc et al. Clin Cancer Res 2011

15 Impact of t(4-14) and del 17p Avet-Loiseau, et al. Blood 2007

16 Avet-Loiseau H et al., leukemia 2007 H. Avet Loiseau et al.

17 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: by American Society of Clinical Oncology

18 P Moreau et al.

19 What about the hyperdiploid status of our patient?

20 Role of imaging in the prognosis of MM?

21 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 2007 Moulopoulos LA, Am J Hematol Merz M, Leukemia 2014 Hillengass J, JCO 2010

22 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

23 Renal impairment?

24 Does age and comorbidities matter?

25 A Simple Score, Based On Geriatric Assessment, Improves Prediction of Survival, and Risk Of Serious Adverse Events In Elderly Newly Diagnosed Multiple Myeloma Patients The higher mortality rate in unfit and frail pts to higher cumulative incidence of grade 3 adverse events in particular extra hematologic toxicities causing subsequent treatment discontinuation. Larocca et al ASH 2013

26 Adaptation des traitements selon la «fragilité» du patient Palumbo A et al. Blood 2011;118:

27 Impact of maximal response Jl Harrousseau; Blood oct 2009

28 Level of CR

29 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

30 Chr 1 abnormalities Avet-Loiseau H, et al. JCO 2012 Hebraud B, et al. Leukemia 2014

31 FISH + ISS model Avet-Loiseau et al Leukemia 2012

32 Critera of myeloma treatement: The near future

33 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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35 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

36 Diagnostic criteria: International Myeloma Working Group Consensus IFM recommendation Palumbo A et al; J Clin Oncol 2014

37 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

38 Belgian consensus recommendations Tablel 3. Examinations at diagnosis Mandatory Recommended Optional Complete blood count, peripheral blood smear, chemistry including calcium and creatinine, beta-2 microglobulin, LDH, serum protein electrophoresis, immunofixation, nephelometric quantification of immunoglobulins. albumin 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. 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. 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. * Recommanded IMMWG 2009 Guidelines for risk stratification in myeloma