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Evidence for use of CT scanning and PET/CT in managing patients with myeloma Elena Evidence for use of CT scanning and PET/CT in managing patients with myeloma Elena Zamagni “Seragnoli” Institute of Hematology Bologna University School of Medicine

ROLE OF IMAGING IN MULTIPLE MYELOMA • Precise identification of bone disease, as sign ROLE OF IMAGING IN MULTIPLE MYELOMA • Precise identification of bone disease, as sign of organ damage and need to start treatment • Identification of sites of extra-medullary disease (total body techniques) • Differential diagnosis between localized disease (BSP) and systemic disease (MM) • Correct identification of sites of bone disease at risk of complications (fractures, neurological complications) (MRI gold standard) • Correct follow up of the patients after treatment, in particular in non secretory MM Zamagni E. et al, BJH 2012

ACTIVE MYELOMA: the CRAB CRITERIA Myeloma-related end organ damage due to the plasma cell ACTIVE MYELOMA: the CRAB CRITERIA Myeloma-related end organ damage due to the plasma cell proliferative process – – C: Calcium levels increased R: Renal insufficiency A: Anemia B: Bone lesions, osteolytic or osteoporosis Rajkumar V. et al. , Lancet Oncology 2014 IMWG, BJH 2003

INTERNATIONAL MYELOMA WORKING GROUP UPDATED CRITERIA FOR THE DIAGNOSIS OF MULTIPLE MYELOMA • Definition INTERNATIONAL MYELOMA WORKING GROUP UPDATED CRITERIA FOR THE DIAGNOSIS OF MULTIPLE MYELOMA • Definition of myeloma bone disease (CRAB): clear evidence of one or more sites of osteolytic bone destruction (at least 5 mm or more in size) seen on CT, WBLDCT, PET/CT, regardless of weather they can be visualized on skeletal radiography or not • If doubt lesions on CT or PET/CT: close follow-up every 3 -6 months and/or biopsy of the lesion • Oseoporosis per se in the absence of lytic lesions is not sufficient for CRAB Rajkumar V. et al. , Lancet Oncology 2014

IMAGING TECHNIQUES IN MM: WBXR Whole body X Ray has always been the standard IMAGING TECHNIQUES IN MM: WBXR Whole body X Ray has always been the standard for the evaluation of bone disease, however: • Lytic lesions are visible only if at least 30%-50% of trabecular substance is lost • Unable to identify small osteolytic lesions (planar technique) • Low sensitivity in the spine • Unable to distinguish between osteoporotic vertebral fractures and MM related ones • It cannot be used for the assessment of response to treatment Frequent underestimation of MM bone disease Zamagni E. et al, BJH 2012 Pianko et al, Clin Canc Res 2014

ROLE OF NEWER IMAGING TECHNIQUES • MORPHOLOGICAL: assessing bone destruction • WB-MDCT-LDCT, CT part ROLE OF NEWER IMAGING TECHNIQUES • MORPHOLOGICAL: assessing bone destruction • WB-MDCT-LDCT, CT part of PET/CT • FUNCTIONAL: assessing bone marrow infiltration and disease metabolism • ASSIAL MRI- WBMRI (DCE-MRI, DWI-MRI), PET/CT • Active MM • at diagnosis: staging and prognosis • after treatment: evaluation of treatment response • Early stage/smoldering MM

WHOLE BODY LOW-DOSE MULTIDETECTOR ROW-CT (WB-LDCT) • Fast scanning time, low radiation dose (3, WHOLE BODY LOW-DOSE MULTIDETECTOR ROW-CT (WB-LDCT) • Fast scanning time, low radiation dose (3, 3 -7 ms. V), high resolution images • Demonstration osseus findings of extra- Shortt CP et al, Sem Musculoskel Radiology 2010 Ippolito D. et al, Eur J Radiol 2013 Wolf MB et al, Eur Journal Radiology 2014 Pianko MJ et al, Clin Canc Res 2014 Horger M. , EJ Radiol, 2004 Hur J. , J Comput Assist Tomogr, 2007

WBLDCT vs WBXR IN THE STAGING OF MM Study Horger EJR 2005 Gleeson Skel WBLDCT vs WBXR IN THE STAGING OF MM Study Horger EJR 2005 Gleeson Skel Radiol 2009 Horger Cancer 2007 Horger BJR 2008 Ippolito EJR 2013 Kropil EJR 2008 Princewill Cancer Invest 2013 Wolf EJR 2014 Study N° pts design Reference test Key findings P 100 NONE P 39 WBXR, WBMRI BM BIOPSY P 131 P 50 R 138 P 29 WBXR WBLDCT > WBXR, in particular in the spine and pelvis. WBXR detected more lesions in the cranium and limbs R 51 WBXR WBLDCT > WBXR 61% of the pts up-staged with WBLDCT WBXR WBLDCT > WBXR, in particular in the axial skeleton. 63% pts up-staged with WBLDCT, 23% pts neg at WBXR and pos at WBCT P Pianko MJ et al. Clin Cancer Res 2014 52 NONE Pioneering study WBLDCT > WBXR, superior detection rate, comparable with WBMRI Response to treatment monitored by WBLDCT NONE Correlation between WBLDCT and hematologic parameters NONE High detection rate of extramedullary findings bone lesions +

ADVANTAGES OF THE USE OF PET/CT IN MM • Capability to identify small osteolytic ADVANTAGES OF THE USE OF PET/CT IN MM • Capability to identify small osteolytic lesions (usual resolution limit: 5 mm) • Possibility to detect both medullary and extramedullary disease and to localize it with anatomic precision by the use of CT • Capability to distinguish between active or inactive disease and/or necrosis-fibrotic tissue • Capability to identify infections or other tumors

EXTRAMEDULLARY DISEASE (EMD) • Need to identify true EMD from para-medullary/breakout lesions • Incidence EXTRAMEDULLARY DISEASE (EMD) • Need to identify true EMD from para-medullary/breakout lesions • Incidence ranging from 7% to 18%; more frequent in later phases of the disease 1, 2 • Increased incidence in the last years due to the availability of more sensitive imaging techniques and the prolongation of survival 1, 2, 3 • Extremely poor prognosis even in the novel agents era 1, 2, 3, 4, 5 • Associated with unfavorable cytogenetic abnormalities and GEP defined high-risk MM 5 • Well assessed by PET/CT and whole body techniques (WB-DWI MRI); in a recent meta-analysis higher sensitivity and diagnostic accuracy of PET/CT for EMD 4 Varettoni M. et al, Annals of Oncology 2010 2 Bladè J. et al, JCO 2011 3 Wale A et al, Haematologica 2016 1 4 5 Lu Y. Y. et al, Clinical Nuclear Med 2012 Usmani S. Z. et al, Haematologica 2012

COMPARISON OF PET OR PET/CT AND CONVENTIONAL IMAGING AT STAGING • 18 studies, 798 COMPARISON OF PET OR PET/CT AND CONVENTIONAL IMAGING AT STAGING • 18 studies, 798 patients • 7 studies PET CT vs WBXR: 6/7 PET showed more lytic lesions with the exception of the skull • 5 studies PET CT vs MRI spine and/or pelvis: 4/5 MRI was superior in detecting myeloma bone disease, especially in case of diffuse bone infiltration • 1 study PET/CT vs WBMRI: concordant in 80% cases • Identification of extra-medullary disease Van Lammeren-Venema D et al. , Cancer 2011

 • 32 directly comparison studies, prospective and retrospective, 1661 patients • Index test • 32 directly comparison studies, prospective and retrospective, 1661 patients • Index test vs reference standard: detection rate • Quality assessment of diagnostic studies • All index tests had sensitivity above 0, 9 as compared to WBXR (low false negative). Fewer additional lesions detected by PET/CT and MRI as compared to WBLDCT can replace WBXR • Modern imaging techniques detected fewer lesions in the skull and ribs «We therefore recommend additional X-ray of the ribs and the skull if clinically relevant» Regelink J. et al. , BJH 2013

Terpos E. et al. , Haematologica 2015 Terpos E. et al. , Haematologica 2015

PROGNOSTIC RELEVANCE OF PET/CT AT DIAGNOSIS (EFS AND OS) IN ASCT CANDIDATES 1, 2, PROGNOSTIC RELEVANCE OF PET/CT AT DIAGNOSIS (EFS AND OS) IN ASCT CANDIDATES 1, 2, 3 • Correlation between imaging techniques and standard prognostic factors in univariate and multivariate analyses; the strongest was PET/CT FLs and beta 2 mic, LDH and CRP 1, 2 • Correlation between PET/CT FLs and GEP derived variables, such as high-risk designation (70 -gene model) and PR subtypes 1, 2 • PET/CT FLs, LDH and cytogenetics abnormalities retained independent prognostic value for PFS and OS in Cox regression analysis 1 Bartel. TB et al, Blood 2009 2 Waheed S et al, Haematologica 2012 3 Usmani S. Z. et al, Blood 2013

PROGNOSTIC VALUE OF PET/CT AT DIAGNOSIS IN ASCT CANDIDATES PFS 64% at 4 yrs PROGNOSTIC VALUE OF PET/CT AT DIAGNOSIS IN ASCT CANDIDATES PFS 64% at 4 yrs SUV ≤ 4. 2 43% at 4 yrs SUV > 4. 2 P= 0. 008 0 12 24 36 48 months 60 72 EMD 84 60% at 4 yrs 25% at 4 yrs P= 0. 0008 12 24 36 48 months Zamagni E. et al, Blood 2011 60 72 84 PFS N° FLs ≤ 3 N° FLs > 3 65% at 4 yrs 43% at 4 yrs P= 0. 01 0 12 24 36 48 months 60 72 EMD PFS Extramedullary neg Extramedullary pos 0 0. 00 0. 20 0. 40 0. 60 0. 80 1. 00 SUV value 0. 00 0. 20 0. 40 0. 60 0. 80 1. 00 N° OF FLs, SUV VALUE, EMD 84 OS 89% at 4 yrs 65% at 4 yrs Extramedullary neg Extramedullary pos P= 0. 006 0 12 24 36 48 months 60 72 84

PROGNOSTIC VALUE OF PET/CT AT STAGING Results reproduced in: • Several independent series of PROGNOSTIC VALUE OF PET/CT AT STAGING Results reproduced in: • Several independent series of patients ASCT candidates, correlating with MRI findings, standard prognostic factors and molecular features of PCs 1, 2, 3, 4 • Small group of patients non ASCT eligible (retrospective study) 5 • Series of patients pre- ALLO SCT (retrospective study) 6 • Re-staging at relapse (retrospective studies) 7, 8 1 Zamagni E. et al, Blood 2011 2 Bartel. TB et al, Blood 2009 3 Waheed S et al, Haematologica 2012 4 Usmani S. Z. et al, Blood 2013 5 Zamagni E. et al, Clin Canc Res 2015 F. et al, Biol BMT 2015 7 Lapa C. et al, Oncotarget 2014 8 Derlin T. et al, EJNM Mol Imag 2011 6 Patriarca

IMAGING TECHNIQUES AT DIAGNOSIS IN ACTIVE MM: WBLDCT PROS CONS • Sensitivity and specificity IMAGING TECHNIQUES AT DIAGNOSIS IN ACTIVE MM: WBLDCT PROS CONS • Sensitivity and specificity • 3 D structural info for CT-guided • biopsy, surgery, RT planning • missed • Can depict EMD, BM involvement, lytic lesions Can assess tumor burden • Rapid acquisition time, Sub-optimal for diffuse bone marrow involvement • • Lesions in ribs and skull may be Few data/unclear prognostic significance of lesion number* low radiation dose • More expensive compared to WBXR • Radiation exposure > WBXR Comfortable for patients • • Inexpensive compared to PET/CT or MRI *Nishida Y et al. , Blood Canc J 2015

IMAGING TECHNIQUES AT DIAGNOSIS IN ACTIVE MM: PET/CT PROS CONS • Sensitivity and specificity IMAGING TECHNIQUES AT DIAGNOSIS IN ACTIVE MM: PET/CT PROS CONS • Sensitivity and specificity • Optimal to assess EMD marrow • Can depict lytic lesions (CT part) lesions • Can assess tumor burden • and Sub-optimal for diffuse involvement and bone skull Cost > WBLDCT, WBXR and MRI disease metabolism • • • Radiation dose > WBXR, WBLDCT Prognostic significance of FLs and • Availability SUV • Useful for staging of SPB

IMAGING TECHNIQUES AT DIAGNOSIS • In both every-day practice and clinical trials WBLDCT is IMAGING TECHNIQUES AT DIAGNOSIS • In both every-day practice and clinical trials WBLDCT is suggested to substitute soon WBXR to define bone end- organ damage • WBXR may be used if WBLDCT is not avaliable • Always consider WBLDCT or PET/CT when WBXR is negative and there is bony pain • PET/CT is a valuable tool for the detection of osteolyses and metabolic lesions predicitng outcomes. Outweight these benefits with economic sustainability • In patients without lytic lesions and CRAB criteria, MRI (at least axial) is recommended for the possible detection of FLs (new diagnostic criteria) Zamagni E. et al, BJH 2012 Pianko MJ et al, Clin Canc Res 2014 Regelink JC et al, BJH 2013 Mesguich C et al, EJR 2014 Terpos E et al, Haematologica 2015 Dimopoulos M et al, JCO 2015

ROLE OF FDG PET/CT IN MULTIPLE MYELOMA • Symptomatic MM • at diagnosis: staging ROLE OF FDG PET/CT IN MULTIPLE MYELOMA • Symptomatic MM • at diagnosis: staging and prognosis • after treatment: evaluation of treatment response, follow-up • Early stage/smoldering MM

METABOLIC RESPONSE TO THERAPY PROGNOSTIC VALUE OF PET/CT BEFORE ASCT Bartel. TB et al, METABOLIC RESPONSE TO THERAPY PROGNOSTIC VALUE OF PET/CT BEFORE ASCT Bartel. TB et al, Blood 2009 • Complete FDG suppression retained independent prognostic value for PFS and OS in Cox regression analysis Usmani S. Z. et al, Blood 2013

METABOLIC RESPONSE TO THERAPY PET-CT normalisation following 3 cycles of RVD Impact on PFS METABOLIC RESPONSE TO THERAPY PET-CT normalisation following 3 cycles of RVD Impact on PFS (32% normalised) 78. 7% 54. 8% p = 0. 04 Moreau P. et al, ASH 2015

METABOLIC RESPONSE TO THERAPY PROGNOSTIC VALUE OF PET/CT AFTER ASCT 0. 00 0. 20 METABOLIC RESPONSE TO THERAPY PROGNOSTIC VALUE OF PET/CT AFTER ASCT 0. 00 0. 20 0. 40 0. 60 0. 80 1. 00 PFS SUV 100% reduction MULTIVARIATE ANALYSIS SUV < 100% reduction VARIABLES HAZARD RATIO (95% CI) P VALUE 15. 43 (4. 11 -57. 95) 0. 000 del (17 p) t(4; 14) 1. 86 (1. 12 -3. 49) 0. 05 Not complete FDG PET suppression 1. 82(1. 19 -3. 77) 0. 01 5. 93 (2. 27 -15. 51) 0. 000 del (17 p) t(4; 14) 1. 90 (1. 09 -3. 32) 0. 023 Not complete FDG PET suppression 1. 89 (1. 06 -3. 35) 0. 030 Relapse 9. 35 (2. 79 -31. 31) 0. 000 Not complete FDG PET suppression 3. 90 (1. 12 -13. 60) 0. 03 47% at 4 yrs 32% at 4 yrs TTP Extramedullary disease P= 0. 02 0 12 24 36 48 60 72 84 96 108 120 months PFS 0. 00 0. 20 0. 40 0. 60 0. 80 1. 00 OS 79% at 4 yrs 66% at 4 yrs OS P= 0. 02 0 12 24 36 48 60 months Zamagni E. et al, Blood 2011 Extramedullary disease 72 84 96 108 120

METABOLIC RESPONSE TO THERAPY PET/CT MRD MONITORING IN CR PATIENTS ASCT eligible and not-eligible METABOLIC RESPONSE TO THERAPY PET/CT MRD MONITORING IN CR PATIENTS ASCT eligible and not-eligible (189 pts) ASCT candidates (192 pts) Zamagni E. et al, Blood 2011 • 70% PET-CR, 40 -50% biochemical CR • 25 -30% of the patients in conventionallydefined CR had PET/CT still positive Zamagni E. et al, Clin Canc Res 2015

METABOLIC RESPONSE TO THERAPY PET-CT normalization before maintenance Impact on PFS (62% normalised) 69% METABOLIC RESPONSE TO THERAPY PET-CT normalization before maintenance Impact on PFS (62% normalised) 69% 51, 6% p < 0. 001 Moreau P. et al, ASH 2015

METABOLIC RESPONSE TO THERAPY PET-CT normalization before maintenance Impact on OS (62% normalised) 94, METABOLIC RESPONSE TO THERAPY PET-CT normalization before maintenance Impact on OS (62% normalised) 94, 6% 69, 9% p = 0. 003 Moreau P. et al, ASH 2015

METABOLIC RESPONSE TO THERAPY PET-CT normalization before maintenance PFS in Arm A: RVD x METABOLIC RESPONSE TO THERAPY PET-CT normalization before maintenance PFS in Arm A: RVD x 8 cycles Adjusted on other prognostic factors p = 0. 009 Univariate log-rank, p = 0. 027 PFS in Arm B: frontline ASCT Adjusted on other prognostic factors p = 0. 01 Univariate log-rank, p = 0. 01 Adjusted on other prognostic factors p = 0. 008 Univariate log-rank, p < 0. 001 Moreau P. et al, ASH 2015 OS in Arm B: frontline ASCT

METABOLIC RESPONSE TO THERAPY PET/CT and MFC MRD MONITORING BEFORE MAINTENANCE PFS 89, 6% METABOLIC RESPONSE TO THERAPY PET/CT and MFC MRD MONITORING BEFORE MAINTENANCE PFS 89, 6% PET/CT and MFC neg 54, 5% PET/CT and/or MFC pos • 86/134 evaluated by both PET/CT and flow • 47, 7% both negative p = 0. 02 Moreau P. et al, ASH 2015

PROGNOSTIC VALUE OF PET/CT AFTER TREATMENT Study Bartel Blood 2009 Study N° pts design PROGNOSTIC VALUE OF PET/CT AFTER TREATMENT Study Bartel Blood 2009 Study N° pts design Treatment PFS OS Cox reg 239 TT 3 PET-CR pre ASCT Yes P 192 Thal-dex + double ASCT PET SUV post induction and PETCR post ASCT PET-CR post ASCT Yes P 302 TT 3 PET FLs (3) day +7 Yes P 19 CHT SUV during CHT / / R 56 Various (CHT, ASCT, novel agents) PET-CR post therapy / / R 47 Novel agents + ASCT in 19 pts MTV post therapy / R 50 Various + ASCT PET-CR post ASCT / Yes for PFS P Zamagni Blood 2011 Usmani Blood 2013 Dimitrakopoulou. Strauss Clin Nucl Med 2009 Eliott EJH 2011 Fonti J Nucl Med 2012 Bakanay ASH 2012 Caldarella C. et al, Int J Mol Imaging 2012

IMAGING TECHNIQUES AFTER TREATMENT: PET/CT PROS CONS • Specificity • Lack of standardization • IMAGING TECHNIQUES AFTER TREATMENT: PET/CT PROS CONS • Specificity • Lack of standardization • Earlier post-therapy changes • Applicability in 75% of the patients • Prognostic • Availability, cost significance in CR patients (MRD monitoring) • Good correlation with biochemical response Zamagni E. et al, BJH 2012 Hillengass J. et al, Leuk and Lymphoma 2013 Mesguich C et al, EJR 2014

IMAGING TECHNIQUES AFTER TREATMENT OPEN ISSUES • Do we need the same imaging technique IMAGING TECHNIQUES AFTER TREATMENT OPEN ISSUES • Do we need the same imaging technique at baseline and after treatment to evaluate metabolic response? • Is the persistence of «severe» positive imaging findings during treatment allowing to change therapy and do we need to evaluate it? • Should we tailor treatment (consolidation/maintenance) on imaging-defined minimal residual disease? • Which relationship between bone marrow MRD and imaging MRD?

FOLLOW-UP PHASE AFTER FIRST-LINE TREATMENT Usefullness of PET/CT follow-up • 282 pts, studied at FOLLOW-UP PHASE AFTER FIRST-LINE TREATMENT Usefullness of PET/CT follow-up • 282 pts, studied at baseline and after treatment (novel agents +/- ASCT) with PET/CT (every 12 -18 months) • • Median follow-up after first-line treatment: 56 months 63% of the patients with relapse/progression: • • • 37% only serologic 48% serologic + skeletal 15% only skeletal • 88% clinical (pain, pathological fractures) and PET/CT • 12% exclusive PET/CT (7% of the pts, 11% of all progressions) Zamagni E. et al, Clin Canc Res 2015

PROGNOSTIC VALUE OF PET/CT AFTER TREATMENT 0 6 months 12 18 24 30 36 PROGNOSTIC VALUE OF PET/CT AFTER TREATMENT 0 6 months 12 18 24 30 36 42 48 54 60 CORRELATION BETWEEN TTP AND SUVmax post ASCT Correlation coefficient = -0, 67, P= 0, 008 Pet suv <4. 2 Pet suv 4. 2 -6 Pet suv 6+ Cuzick’s trend test P= 0, 017 FACTORS ASSOCIATED WITH EXCLUSIVE PET/CT PROGRESSION AFTER FIRST-LINE THERAPY: A LOGISTIC REGRESSION RESULTS OR SUV > 4. 2 after 1° line treatment Nanni C. et al, Clin Nuclear Medicine 2012 95% CI p 4. 17 1. 01 -17. 41 0. 05 Zamagni E. et al, Clin Canc Res 2015

NEWER IMAGING TECHNIQUES: FOLLOW -UP POST TREATMENT • Serial evaluation with novel imaging techniques NEWER IMAGING TECHNIQUES: FOLLOW -UP POST TREATMENT • Serial evaluation with novel imaging techniques (PET/CT or WBMRI) after first line treatment is currently not recommended to all the patients because of the high costs (monetary and radiation exposure) and low usefulness. Our analysis confirm this suggestion • In the small subgroup of patients with a persistent high glucose metabolism after first-line treatment (approximately 10%), serial PET/CT evaluation can be recommended during the follow-up, in order to point-out possible progression not otherwise identifiable

ROLE OF FDG PET/CT IN MULTIPLE MYELOMA • Symptomatic MM • at diagnosis: staging ROLE OF FDG PET/CT IN MULTIPLE MYELOMA • Symptomatic MM • at diagnosis: staging and prognosis • after treatment: evaluation of treatment response, follow-up • Early stage/smoldering MM

TTP PET/CT neg (97 pts): 30% at 2 yrs PET/CT neg: median 60 mos TTP PET/CT neg (97 pts): 30% at 2 yrs PET/CT neg: median 60 mos PET/CT pos (74 pts): 75% at 2 yrs PET/CT pos with osteolyses (16 pts): median 21 mos (87% at 2 yrs) p = 0. 0008 Siontis B. et al, Blood Cancer J 2015 p = 0. 004

PROGNOSTIC ROLE OF FLs WITHOUT OSTEOLYSES IN SMM 100 Time to progression of SMM PROGNOSTIC ROLE OF FLs WITHOUT OSTEOLYSES IN SMM 100 Time to progression of SMM to active MM 75 Median 4, 5 yrs PET/CT negative 50 Median 1, 1 yr 25 PET/CT positive 0 HR 3. 00 (95% CI 1. 58 -5. 69) p=0. 001 0 1 2 Years 3 4 Prospective study on 120 pts, median f up 2, 2 years Centralized imaging revision 16% pts with FLs, without underlying osteolytic lesions Probability of progression at 2 years PET/CT pos pts vs neg: 58% vs 33% Zamagni E. et al. , Leukemia 2015

EXTENSIVE USE OF NEWER IMAGING TECHNIQUES OPEN ISSUES • Quality of many studies hampered EXTENSIVE USE OF NEWER IMAGING TECHNIQUES OPEN ISSUES • Quality of many studies hampered by a poor description of selection and execution criteria • Major inconsistency in methodology between studies • Need to define standardized criteria for definitions and positivity cut-off imaging • IMWG prospective study on WBLDCT • Italian/European proposal for PET/CT interpretative criteria (Nanni C et al, EJNM 2015) Zamagni E. et al, BJH 2012 Pianko MJ et al, Clin Canc Res 2014 Regelink JC et al, BJH 2013 Mesguich C et al, EJR 2014

Description, in a 5 points scale, of: Bone Marrow metabolic state (BM) Number and Description, in a 5 points scale, of: Bone Marrow metabolic state (BM) Number and site of Focal Lesions (Fx) with or without Osteolytic Lesions (Lx) Presence and site of Extramedullary Disease (EM) Presence of Paramedullary Disease (PM) Presence of Fractures (Fr) A visual degree of uptake is defined for the target lesion and extramedullary lesions according to the scheme proposed in Deauville Criteria for the evaluation of lymphoma patients Nanni C. et al. , EJNM 2015

CONCLUSION • Newer imaging techniques have proved reliable tools in the staging and as CONCLUSION • Newer imaging techniques have proved reliable tools in the staging and as predictors of outcome in MM patients, both in early stage and active disease • At diagnosis, WBLDCT is suggested to substitute in the near future WBXR • PET/CT and DWI-MRI are the favorite techniques for assessing and monitoring response to therapy and are becoming complementary investigation tools for detecting minimal residual disease, going beyond the conventionally defined CR level • Implementation of prospective clinical trials with newer imaging techniques will help to adress several issues, standardize the interpretation of the results and optimize the use of these promising tools. This may improve disease management