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Should we treat SMM?

NO!

Xavier Leleu

Hôpital la Milétrie, PRC, CHUInserm U1402 CIC

Laboratoire d’Immunologie Oncologie et dormance tumoralePoitiers, France

Disclosures

• Honorarium, Grants/research support, and Consulting fees:

Amgen, Celgene, Janssen, Takeda, Novartis, Sanofi, Merck, Pierre Fabre, Mundipharma, Karyopharm, Roche, Abbvie, Bristol-Myers Squibb,

Lenalidomide + Dex

No treatment

Lenalidomide + Dex: 98% at 3 yearsNo treatment: 82% at 3 years

Time from inclusion

Len-dex vs no treatment: OS from inclusion(n = 118)

Prop

ortio

n of

pat

ient

s al

ive

4035302520151050

1.0

0.8

0.6

0.4

0.2

0.0

p=0.05

Median follow-up: 22 months (range 5–42)

5

1,0

0,8

0,6

0,4

0,2

0,0

24211815129630

Lendex

No treatmentMedian TTP: 19.3 m

p<0,0001

Progression to MM

How to avoid ?

How to identify?

Risk of SMM: QuiRedex

1 pt IC withdrawal during the 1st cycle 1 pt discontinuation after the 8th cycle

6 pts : lytic lesions3 pts : lytic lesions plus anemia1 pt : lytic lesions, renal insufficiency & hypercalcemia5 pts: anemia

6

SMM is not an homogeneous group

Kyle R et al. N Engl J Med 2007;356:2582‐2590

Patients with >10% BM plasma cells AND M Comp >30g/l = Group 1

8 yr

2 yr

19 yr

NOT SMM

(nice try…)

61 years old male, routine lab test ESR elevated

Prior history. None Clinically. None CBC normal but Hb 11.1g/dL CREATININE normal; Calcium

normal; LDH normal; B2M 4.1mg/L SPEP 45g/L M-spike; IgA L IFS sFLC k 300, r 85; No proteinuria BM aspiration 40%, no del17p, no

t(4;14), 1 abn MRI normal R-ISS would be 2

61 years old male, routine lab test ESR elevated

Prior history. None Clinically. None CBC normal but Hb 13g/dL CREATININE normal; Calcium

normal; LDH normal; B2M 2.3mg/L SPEP 30g/L M-spike; IgG K IFS sFLC normal; No proteinuria BM aspiration 12%, no del17p, no

t(4;14), 1 abn MRI normal R-ISS would be 1

Smoldering multiple myeloma: early treatment

Conventional agentsInitial MP vs

Deferred MP1,2,3 No benefit in ORR/TTP/OS

Novel agents

Thalidomide4,5~ 30% ≥ PR; high toxicity;

patients achieving PR had a shorter time to treatment

Bisphosphonates vs abstention 6,7

No benefit in ORR/TTP/OSLower incidence of skeletal related events

1.Hjorth M, et al. Eur J Haematol. 1993;50:95-102. 2.Grignani G, et al. Br J Cancer. 1996;73:1101-07. 3.Riccardi A, et al. Br J Cancer. 2000;82:1254-60.

4. Rajkumar SV, et al. Am J Hematol 2010; 85(10):737-405. Barlogie B, et al. Blood. 2008;112:3122-25. 6. Musto P, et al. Leuk Lymphoma. 2011;52(5):771-7757. Musto P, et al. Cancer. 2008;113:1588-95.

INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY). 10

Scre

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1:1:

1 R

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ON Cycle 1:

QWCycles 2 & 3:

Q2WCycles 4-7:

Q4WCycles 8-20:

Q8W

Cycle 1: QW

Cycles 2-20: Q8W

n = 41

n = 41

n = 41

Arm A (16 mg/kg IV; 8-week cycles); Long Intense (max 3 years)

Arm B (16 mg/kg IV; 8-week cycles); Intermediate (max 3 years)

Arm C (16 mg/kg IV; one 8-week cycle); Short Intense

Following until PD or end of study

(4 years from LPFD)

Primary endpoints:• CR• % patients with

PDa or death per patient-yearCycle 1:

QW

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

CENTAURUS Study Design

aAs defined by 2014 IMWG criteria for smoldering multiple myeloma.

• CR rate: proportion of subjects who achieve a CR in each arm– First assessed 6 months after last patient randomized

• PD/death rate: ratio of subjects with an event (PD or death) to the total follow-up for all patients– Assessed 12 months after last patient randomized– Disease progression to MM assessed according to IMWG guidelines1

GEM-CESAR: Study Design• Multicenter, open-label, phase II trial

Induction6 x 28-day

cycles

High-risk was defined according to the Mayo and/or Spanish models-Patients with any one or more of the biomarkers predicting imminent risk of progression to MM were allowed to be included but…-New imaging assessments were mandatory at screening and if bone disease was detected in the CT or PET-CT, patients were excluded

High-risk* Smouldering MM patients

Carfilzomib i.v.20/36 mg/m2

Days 1, 2, 8, 9, 15, 16

Lenalidomide25 mg

Days 1–21

Dexa 40 mgDays 1, 8, 15 & 22


Days 1, 2, 8, 9, 15, 16

Lenalidomide25 mg

Days 1–21

Dexa 40 mgDays 1, 8, 15 & 22

High-dose Melphalan[200 mg/m2]Followed by

ASCT

High-dose Melphalan[200 mg/m2]Followed by

ASCT


Days 1, 2, 8, 9, 15, 16

Lenalidomide25 mg

Days 1–21

Dexa40 mgDays 1, 8, 15 & 22


Days 1, 2, 8, 9, 15, 16

Lenalidomide25 mg

Days 1–21

Dexa40 mgDays 1, 8, 15 & 22

Consolidation2 x 28-day

cycles

Lenalidomide10 mg

Days 1–21

Dexamethasone

20 mgDays 1, 8, 15

& 22

Lenalidomide10 mg

Days 1–21

Dexamethasone

20 mgDays 1, 8, 15

& 22

Maintenance24 x 28-day

cycles

N=35 N=29

Mateos M-V, et al. Presented at ASH 2017 (Abstract 402), oral presentation.

Should we treat SMM ? = NO

Leukemia 2010

JCO 2010

Never give up!

Thank you for your attention

Xavier, please set me free…

*Myeloma-related organ or tissue impairment (end-organ damage) related to plasma cell proliferative process: anaemia with 2 g/dL below the normal level or <10 g/dL, or serum calcium level >10 mg/L (0.25 mmol/L) above normal or>110 mg/dL (2.75 mmol/L), or lytic bone lesions or osteoporosis with compressive fractures, or renal insufficiency (creatinine >2 mg/dL or 173 mmol/L), [CRAB: Calcium increase, Renal impairment, Anaemia and Bone lesion] or symptomatic hyperviscosity, amyloidosis or recurrent bacterial infections (>2 episodes in 12 months);†For symptomatic MM, a minimum level of M-component or BMPC infiltration (although usually it is >10%) is not required; provided that these two features coexists with the presence of end-organ damageIMWG, International Myeloma Working Group

International Myeloma Working Group. Br J Haematol 2003;121:749–757; Kyle R, et al. Leukemia 2010;24:1121–1127

IMWG criteria for the classification of monoclonal gammopathies

Monoclonalgammopathy of uncertain significance(MGUS) SMM Symptomatic MM

Monoclonal (M)component <30 g/L serum ≥30 g/L serum Present

(serum/urine)AND AND/OR AND

Bone marrowplasma cells (BMPCs; %)

<10% ≥10% >10%†

AND AND ANDEnd-organ Damage* Absent Absent Present

INTENDED FOR INTERNAL USE. ALL MATERIALS/CONTENT ARE SUBJECT TO RELEVANT LOCAL REVIEW PROCESSES (IE, MEDICAL, LEGAL, COMPLIANCE, PRIVACY AND REGULATORY).

Daratumumab Monotherapy for Patients With Intermediate or High‐risk Smoldering Multiple

Myeloma (SMM): CENTAURUS, a Randomized, Open‐Label, Multicenter Phase 2 Study

Craig C. Hofmeister, Ajai Chari, Yael C. Cohen, Andrew Spencer, Peter Voorhees, Jane Estell, Christopher Venner, Irwindeep Sandhu,Matthew Jenner, Catherine Williams, Michele Cavo, Niels W.C.J. van de Donk, Meral Beksac, Steven Kuppens, Rajesh Bandekar, Tobias Neff, Christoph Heuck, Ming Qi, Hartmut Goldschmidt, C. Ola

Landgren

Oral presentationSession Name: Myeloma: Therapy, Excluding Transplantation: Immunotherapy in Myeloma and AmyloidSession Date: Sunday, 10 December 2017 Session Time: 4:30 – 6:00PM

Presenter: Tobias Neff, MD


Scre

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1:1:

1 R

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DO

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ON Cycle 1:

QWCycles 2 & 3:

Q2WCycles 4-7:

Q4WCycles 8-20:

Q8W

Cycle 1: QW

Cycles 2-20: Q8W

n = 41

n = 41

n = 41

Arm A (16 mg/kg IV; 8-week cycles); Long Intense (max 3 years)

Arm B (16 mg/kg IV; 8-week cycles); Intermediate (max 3 years)

Arm C (16 mg/kg IV; one 8-week cycle); Short Intense

Following until PD or end of study

(4 years from LPFD)

Primary endpoints:• CR• % patients with

PDa or death per patient-yearCycle 1:

QW

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

CENTAURUS Study Design

aAs defined by 2014 IMWG criteria for smoldering multiple myeloma.

• CR rate: proportion of subjects who achieve a CR in each arm– First assessed 6 months after last patient randomized



Progression-Free Survival

% s

urvi

ving

with

out p

rogr

essi

on

0

20

40

60

80

100

0 3 6 9 12 15 18 24Months

21

Arm B: IntermediateArm A: Long intense

Arm C: Short intense

414141

414140

403635

393631

373224

211916

1286

000

111

No. at riskLong intenseIntermediate

Short intense

Post-hoc analysis comparing Arm A + Arm B versus Arm C: P value = 0.0398

Extended Daratumumab Therapy Prolongs PFS

Study arm 12-month PFS rate

Progressionto MM based

on SLiMCRABcriteria, n

Arm ALong Intense 95% 3

Arm BIntermediate 88% 5

Arm CShort Intense 81% 9


0

20

40

60

80

100

0 3 6 9 12 15 18 24Months

21

414141

414140

403430

393325

362818

211613

1275

000

111

No. at riskLong intenseIntermediate

Short intense

Arm B: Intermediate

Arm A: Long intense

Arm C: Short intense

Biochemical/diagnostic PFS is defined as the earlier of time to biochemical or diagnostic progression or death

Post-hoc analysis comparing Arm A + Arm B versus Arm C: P = 0.0002

Biochemical/Diagnostic Progression-Free Survival

Extended Daratumumab Therapy Prolongs Biochemical/Diagnostic PFS

Study arm 12-monthPFS rate

Arm ALong Intense 90%

Arm BIntermediate 76%

Arm CShort Intense 54%

Smoldering MM

María-Victoria Mateos

Zinc code: PHEM/HEM/1217/0001bDate of preparation: December 2017

Risk of progression associated with MYC alterations

Keane N, et al. Presented at ASH 2017 (Abstract 393), oral presentation.

MYC-IG translocations may predict high risk of rapid progression from SMM to MM– 100% of cases progressed within

2 years

Time to progression by IG-MYC SVTime to progression by MYC SV

SV, structural variants; TPP, time to progression

96 patients with SMM, median age 63 years

MYC SVs at SMM predict shorter median TTP– 23 versus 50 months

GEM-CESAR: Consolidation & Maintenance: Efficacy (35/29 pts)

Response category Induction

(n=71)

HDT-ASCT(n=42)

Consolidation

(n=35)

Maintenance

(n=29)

ORR 69 (98%)

42 (100%) 35 (100%) 29 (100%)

sCR 21 (30%)

22 (52%) 24 (69%) 24 (83%)

CR 9 (13%) 2 (5%) 2 (6%) 2 (7%)VGPR 27

(38%)12 (29%) 7 (20%) 2 (7%)

PR 12 (17%)

6 (14%) 2 (6%) 1 (3%)

SDMRD –ve, 31% 50% 60% N/ARelapse from CR 2 (3%) - - -Clinical progression - - - -

* No patients discontinued consolidation ormaintenance

Mateos M-V, et al. Presented at ASH 2017 (Abstract 402), oral presentation.

Phase 2 CENTAURUS study: daratumumab in SMM

Hofmeister C, et al. Presented at ASH 2017 (Abstract 510), oral presentation.

Scre

enin

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1:1:

1 R

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DO

MIZ

ATI

ON Cycle 1:

QWCycles 2 & 3:

Q2WCycles 4-7:

Q4W

Cycles 8-20:

Q8W

Cycle 1: QW

Cycles 2-20: Q8W

n = 41

n = 41

n = 41

Arm A (16 mg/kg IV; 8-week cycles); Long

Arm B (16 mg/kg IV; 8-week cycles); Intermediate

Arm C (16 mg/kg IV; one 8-week cycle); Short

Following until PD or

end of study (4 years from

LPFD)

Primary endpoints:• CR• % patients

with PDa or death per patient-year

Cycle 1:

QW

• CR rate: proportion of subjects who achieve CR in each arm– First assessed 6 months after last patient randomized


• Pre-infusion medication: methylprednisolone 60-100 mg, diphenhydramine 25-50 mg, acetaminophen 650-1,000 mg, montelukast 10 mg (optional)

aAs defined by 2014 IMWG criteria for SMM.

IV, intravenous; QW, once weekly; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; PD, progressive disease; LPFD, last patient, first dose; CR, complete response.1 R jk SV t l L t O l 2014 15 538 548

CENTAURUS: Efficacy

Hofmeister C, et al. Presented at ASH 2017 (Abstract 510), oral presentation.ORR, overall response rate; PR, partial response; VGPR, very good partial response; PFS, progression free survival

aPD/death rate is the ratio of the patients who progressed or died divided by the total PFS for all patients. bP value for testing the null hypothesis that the PD/death rate ≥0.346/patient-year (corresponding to median PFS ≥24 months).

Co-primary endpoint of CR (>15%) was not met

PD/Death Ratea

Arm ALong

(n = 41)

Arm BIntermedi

ate(n = 41)

Arm CShort

(n = 41)

P valueb <0.0001 <0.0001 0.0213

≥VGPR:29%

≥VGPR:24%

≥VGPR:15%

ORR = 56%ORR = 54%

ORR = 38%

ORR

Arm ALong

(n = 41)

Arm BIntermediate

(n = 41)

Arm CShort

(n = 40)

Co-primary endpoint of median PFS ≥24 months was met

Single-agent daratumumab shows activity in SMM

CENTAURUS: PFS (Based on SLiM-CRAB)

Hofmeister C, et al. Presented at ASH 2017 (Abstract 510), oral presentation.

Fewer patients progressed on long and intermediate arms

% s

urvi

ving

with

out p

rogr

essi

on

0

20

40

60

80

100

0 3 6 9 12 15 18 24Months

21

Arm B: IntermediateArm A: Long

Arm C: Short

414141

414140

403635

393631

373224

211916

1286

000

111

No. at riskLong

IntermediateShort

• Post-hoc analysis comparing Arm A + Arm B versus Arm C: P value = 0.0398

Study arm 12-month PFS rate

Arm A: Long 95%

Arm B: Intermediate 88%

Arm C: Short 81%

IRR, infusion-related reaction; TEAE, treatment-emergent adverse event; SPM, secondary primary malignancy.

Arm ALong

(n = 41)

Arm BIntermediate

(n = 41)

Arm CShort

(n = 40)

Median (range) duration of treatment, months

14.9 (1.0-22.1)

14.8 (1.9-22.1)

1.6 (0-1.9)

Grade 3/4 TEAE, n (%) 15 (37) 4 (10) 6 (15)

Most common (>25%) any-grade TEAE, n (%)

FatigueCoughUpper respiratory tract infectionInsomniaHeadache

16 (39)14 (34)11 (27)11 (27)11 (27)

25 (61)13 (32)11 (27)13 (32)8 (20)

9 (23)11 (28)4 (10)5 (13)13 (33)

Most common (>1 pt) grade 3/4 TEAE, n (%)HypertensionHyperglycemia

2 (5)1 (2)

1 (2)2 (5)

1 (3)0 (0)

Serious adverse events, n (%)Within the first 8 weeks

10 (24)5 (12)

1 (2)0 (0)

4 (10)4 (10)

Discontinued treatment due to TEAE, n (%)Related to daratumumab

2 (5)1 (2)a

1 (2)0 (0)

2 (5)1 (3)b

Any-grade IRR rate, n (%) 23 (56) 17 (42) 22 (55)

Hematologic TEAE rate was <10% across all arms

Rates of grade 3/4 infection were ≤5% across all arms

1 death due to disease progression in Arm C

3 SPMs (Arm A: breast cancer, melanoma; Arm B: melanoma)Findings are consistent with other single-agent

daratumumab studies

CENTAURUS: Safety

aThrombocytopenia; bUnstable angina.

Phase 2 study:siltuximab (anti IL-6 mAb) in smoldering MM 85 patients with intermediate- or

ultra-high-risk SMM Median age 61–62 years; more

patients in placebo group had ultra-high-risk SMM or cytogenetic abnormalities than in siltuximab group

Median follow-up: 29.2 months 1-year PFS rate was 84.5% with

siltuximab group vs 74.4% with placebo

Siltuximab was well tolerated

Brighton T, et al. Presented at ASH 2017 (Abstract 3155), poster presentation.

PFS

HR: 0.503; 95% CI: 0.243, 1.042; p=0.0597

Siltuximab may delay disease progression in high-risk SMM

however, pre-specified hypothesis of 14% increase in 1-

year PFS was not met

Frontline:Transplant-ineligible

María-Victoria Mateos

EMN01 phase 3 study: Rd vs MPR vs CPR induction followed by RP vs R as maintenance in NDMM

Bringhen S, et al. Presented at ASH 2017 (Abstract 901), oral presentation.

EMN01 phase 3 study: Rd vs MPR vs CPR induction followed by RP vs R as maintenance in NDMM

Bringhen S, et al. Presented at ASH 2017 (Abstract 901), oral presentation.

Progression-free survival from start of maintenance Median age 73 years

The addition of prednisone to lenalidomide maintenance improved PFS

Gimema-MM-03-05 and EMN01 studies:V-based vs R-based induction in high-risk patients

Larocca A, et al. Presented at ASH 2017 (Abstract 744), oral presentation.

Gimema-MM-03-05 and EMN01 studies:V-based or R-based induction in high-risk patients

Larocca A, et al. Presented at ASH 2017 (Abstract 744), oral presentation.

BORT (N=511) vs LEN (N=654)VMP (N=257) vs Rd (N=217)

Median age 71–73 years years Standard risk: VMP 52%, Rd 60% High risk: VMP 21%, Rd 21%

Median age 71–73 years Standard risk: VMP 53%, Rd 63% High risk: VMP 19%, Rd 22%

HOVON-126/NMSG 21.13 study: ITd induction followed by ixazomib maintenance in NDMM

Zweegman S, et al. Presented at ASH 2017 (Abstract 433), oral presentation.

Ixazomib 4 mg, days 1, 8, 15Thalidomide 100 mg, days 1–28Dexamethasone 40 mg, days 1,

8, 15, 22

Ixazomib 4 mgdays 1, 8, 15

Placebodays 1, 8, 15Nine 28-day induction

cycles

28-day cyclesuntil progression

• High-risk cytogenetics defined as del17p, t(4;14), or t(14;16)

HOVON-126/NMSG 21.13 study: ITd induction followed by ixazomib maintenance in NDMM

Zweegman S, et al. Presented at ASH 2017 (Abstract 433), oral presentation.

Response rate (%) ITT(n=120

)

Cytogenetic risk

Modified IMWG frailty

Standard

(n=83)

High(n=19)

Fit(21%)

Unfit(28%)

Frail(47%)

Overall response on induction 81 84 79 88 85 75CR 10 - - - - -VGPR 34 - - - - -PR 37 - - - - -≥ CR 10 10 11 16 9 9≥ VGPR 44 48 42 36 53 43Median time to response (mo) 1.1 - - - - -Median time to maximum response (mo)

4.7 - - - - -

Phase 1b study of isatuximab + VCD in NDMM 17 patients, median age 70.0–72.5 years MTD not reached IARs were reported in 8/17 patients (47%), were generally Grade 1/2 in

severity and all occurred during the first infusion ORR was 93% of patients; ≥VGPR in 73%

Ocio EM, et al. Presented at ASH 2017 (Abstract 3160), poster presentation.

Progression-free survival by NGF MRD levels

Time on treatment by best confirmed respons

Isatuximab + VCD is clinically active in NDMM

Safety profile is generally consistent with those of the

individual agents

ALCYONE Study Design

Mateos MV, et al. Presented at ASH 2017 (Abstract LBA-4), oral presentation.

NDMM, newly diagnosed multiple myeloma; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; EU, European Union; VMP, bortezomib/melphalan/prednisone; SC, subcutaneously; PO, orally; D, daratumumab; IV, intravenously; PD progressive disease; PFS progression-free survival; ORR overall response rate; VGPR very good

Key eligibility criteria:

•Transplant-ineligible NDMM•ECOG 0-2•Creatinine clearance ≥40

mL/min•No peripheral neuropathy grade ≥2

Stratification factors

•ISS (I vs II vs III)•Region (EU vs other)•Age (<75 vs ≥75 years)

1:1

Ran

dom

izat

ion

(N =

706

)

D-VMP × 9 cycles (n = 350)

Daratumumab: 16 mg/kg IVCycle 1: once

weeklyCycles 2-9: every

3 weeks

+

Same VMP schedule

Follow-up for

PD and

survival

Primary endpoint:

•PFS

Secondary endpoints:

•ORR•≥VGPR rate•≥CR rate•MRD (NGS; 10–5)•OS•Safety

VMP × 9 cycles (n = 356)

Bortezomib: 1.3 mg/m2 SC Cycle 1: twice weeklyCycles 2-9: once weekly Melphalan: 9 mg/m2 PO on Days 1-4 Prednisone: 60 mg/m2 PO on Days 1-4 D

Cycles 10+

16 mg/kg IV

Every4 weeks: until PD

Statistical analyses• 360 PFS events: 85%

power for 8-month PFS improvement

• Interim analysis: ~216 PFS events

• Cycles 1-9: 6-week cycles• Cycles 10+: 4-week cycles

Efficacy: PFS


50% reduction in the risk of progression or death in patients receiving D-VMP

PFS, progression-free survival; VMP, bortezomib/melphalan/prednisone;D, daratumumab; HR, hazard ratio; CI, confidence interval.aKaplan-Meier estimate.

% s

urvi

ving

with

out p

rogr

essi

on

0

20

40

60

80

0 3 6 9 12 15 18 27Months

356350

303322

276312

261298

231285

127179

6193

00

210

No. at riskVMP

D-VMP

21 24

1835

12-month PFSa18-month PFSa

HR, 0.50 (95% CI, 0.38-0.65; P <0.0001)

VMPMedian: 18.1 months

D-VMPMedian: not reached

87%

72%76%

50%

100

• Median (range) follow-up: 16.5 (0.1-28.1) months

Efficacy: PFS in Prespecified Subgroups


PFS, progression-free survival; VMP, bortezomib/melphalan/prednisone; D, daratumumab; CI, confidence interval; NE, not evaluable; CrCl, creatinine clearance; ISS, International Staging System; MM, multiple myeloma; Ig, immunoglobulin; ECOG, Eastern Cooperative Oncology Group.aPatients with measurable disease in serum. b95% of patients IgA.

D-VMP prolonged PFS across all subgroups analyzedFavor D-VMP Favor VMP

Hazard ratio (95% CI)Median

(months)Median (months)

19.113.5

NENE

0.53 (0.40, 0.71)0.42 (0.22, 0.80)

Baseline hepatic functionNormalImpaired

30352

30146

19.417.516.8

NENENE

0.50 (0.24, 1.05)0.49 (0.32, 0.73)0.53 (0.35, 0.79)

ISS stagingIIIIII

67160129

69139142

18.117.4

18.0NE

0.78 (0.43, 1.43)0.39 (0.28, 0.55)

Cytogenetic riskHigh riskStandard risk

45257

53261

19.417.6

NENE

0.40 (0.21, 0.74)0.52 (0.39, 0.70)

ECOG performancestatus01-2

99257

78272

17.4NE

NENE

0.45 (0.32, 0.64)0.81 (0.48, 1.37)

Type of MMIgGNon-IgGa,b

21883

20782

n n

VMP D-VMP

0.1 1 10

Hazard ratio (95% CI)Median (months)

Median (months)

18.117.9

NENE

0.60 (0.42, 0.87)0.41 (0.28, 0.61)

SexMaleFemale

167189

160190

17.920.4

NENE

0.49 (0.36, 0.68)0.53 (0.32, 0.85)

Age<75 years≥75 years

249107

246104

18.116.8

NENE

0.56 (0.42, 0.74)0.26 (0.12, 0.57)

RaceWhiteOther

30452

29753

18.316.9

NENE

0.63 (0.45, 0.88)0.36 (0.24, 0.56)

Baseline renal function (CrCl)

>60 mL/min≤60 mL/min

211145

200150

17.5 NE 0.22 (0.10, 0.50)18.1 NE 0.57 (0.43, 0.76)

RegionEuropeOther

29561

28961

n n

VMP D-VMP

0.1 1 10

Favor D-VMP Favor VMP

Efficacy: ORRa

Median duration of response: 21.3 months in VMP versus not reached in D-VMP


ORR, overall response rate; VMP, bortezomib/melphalan/prednisone; D, daratumumab; CR, complete response; VGPR, very good partial response; PR, partial response; sCR, stringent complete response.aIntent-to-treat population. bP value was calculated with the use of the Cochran–Mantel–Haenszel chi-square test. cP <0.0001. dResponders in response-evaluable population.

Significantly higher ORR, ≥VGPR rate, and ≥CR rate with D-VMP;>2-fold increase in rate of sCR with D-VMP

VMP(n =

263)d

D-VMP(n =

318)d

Median (range)time to firstresponse, months

0.82(0.7-12.6)

0.79(0.4-15.5)

Median (range) time to bestresponse, months

4.11(0.7-20.5)

4.93(0.5-21.0)

P <0.0001

ORR = 74%

ORR = 91%

≥CR:24%b,c

≥VGPR:50%b,c

≥CR:43%

≥VGPR:

71%

6

22

0

5

10

15

20

25

VMP (n = 356) D-VMP (n = 350)

MR

D-n

egat

ive

rate

, %Efficacy: MRDa (NGS; 10–5 Sensitivity Threshold)


MRD, minimal residual disease; NGS, next-generation sequencing using clonoSEQ version 2.0 (Adaptive); VMP, bortezomib/melphalan/prednisone; D, daratumumab; CR, complete response ; sCR stringent complete response. aA d t ti f fi ti f CR/ CR d if fi d 12 18 24 d 30 th

P <0.0001

3.6X

>3-fold higher MRD-negativity rate with D-VMP; Lower risk of progression or death in all MRD-negative patients

• Median (range) follow-up: 16.5 (0.1-28.1) months

% s

urvi

ving

with

out p

rogr

essi

on

0

20

40

60

80

100

0 3 6 9 12 15 18 27Months

2278

334272

2278

281244

2278

254234

2277

239221

2175

210210

1458

113121

8315362

0000

0228

No. at riskVMP MRD negative

D-VMP MRD negativeVMP MRD positive

D-VMP MRD positive

21 24

4141421

VMP MRD negative

VMP MRD positive

D-VMP MRD negative

D-VMP MRD positive

Efficacy: OS

Mateos MV, et al. Presented at ASH 2017 (Abstract LBA-4), oral presentation.OS, overall survival; VMP, bortezomib/melphalan/prednisone; D, daratumumab.

VMP (n = 356)

D-VMP(n = 350)

Events, n (%) 48 (13.5) 45 (12.9)

• Median survival was not reached in either treatment arm

Data are immature after median follow-up of 16.5 months

Safety: Most Common TEAEsa

1 patient in each arm discontinued treatment due to pneumonia

1.4% and 0.9% of patients receiving VMP and D-VMP, respectively, discontinued treatment due to infection

Mateos MV, et al. Presented at ASH 2017 (Abstract LBA-4), oral presentation.TEAE, treatment-emergent adverse event; VMP, bortezomib/melphalan/prednisone; D, daratumumab.aAny grade TEAEs in ≥20% of patients and grade 3 or 4 TEAEs in ≥10% of patients in either

VMP (n = 354) D-VMP (n = 346)

Any Grade

Grade 3 or 4

Any Grade

Grade 3 or 4

Hematologic, n (%)

Neutropenia 186 (53) 137 (39) 172 (50) 138 (40)

Thrombocytopenia 190 (54) 133 (38) 169 (49) 119 (34)

Anemia 133 (38) 70 (20) 97 (28) 55 (16)

Nonhematologic, n (%)

Peripheral sensory neuropathy 121 (34) 14 (4) 98 (28) 5 (1)

Upper respiratory tract infection 49 (14) 5 (1) 91 (26) 7 (2)

Diarrhea 87 (25) 11 (3) 82 (24) 9 (3)

Pyrexia 74 (21) 2 (1) 80 (23) 2 (1)

Nausea 76 (22) 4 (1) 72 (21) 3 (1)

Pneumonia 17 (5) 14 (4) 53 (15) 39 (11)VMP (n = 354) D-VMP (n = 346)

Deaths due to TEAEs, n (%) 19 (5) 19 (6)

Safety: IRRs

Most IRRs occurred during the first infusion 5 (1.4%) patients discontinued daratumumab due to

IRRs Montelukast was allowed as additional premedication

and was used in <5% of patients

Mateos MV, et al. Presented at ASH 2017 (Abstract LBA-4), oral presentation.IRR, infusion-related reaction; D, daratumumab; VMP, b t ib/ l h l / d i

D-VMP (n = 346)

All Grades Grade 3 Grade 4 Grade 5Patients with IRRs, n (%) 96 (28) 15 (4) 2 (1) 0

Panel discussion: possible questions

• With the advent of the new IMWG diagnostic criteria, what lies between MGUS and myeloma?

• What are the treatment goals for these patients and how should they be treated (less intense versus modern combinations)?

• Which SMM patients would be good candidates for Daratumuab monotherapy, i.e. CENTAURUS

• How are we going to integrate Dara-VMP into clinical practice? Which patients would you treat with this regimen?

Slide not shown

Kyle RA, et al. N Engl J Med. 2007; 356:2582-90Dispenzieri A, et al. Blood. 2008;111:785-9.

Smoldering MM: PCs BM infiltration and serum M-component level plus sFLC ratio

Gr 1:TTP 1.9 y

Gr 2: TTP: 5 y

Gr 3: TTP 10 y

p < 0.001100

80

60

40

20

00 5 10 15

Prob

abili

ty o

f Pr

ogre

ssio

n (%

)

Years

No. of risk factors No. Rel risk

1 81 12 114 1.9 (1.2–2.9)3 78 4.0 (2.6–6.1)

• PCsBM Infiltration ≥ 10%• Serum M protein ≥ 3 g/dL• Serum FLC ratio < 1/8 or > 8

Perez-Persona E, et al. Blood. 2007;110:2586-92.

Smoldering multiple myeloma: aberrant PCs by immunophenotype plus immunoparesis

> 95% aPC/BMPC or paresisn = 22 (10 progr.)

>95% aPC/BMPC + paresisn = 39 (28 progr.)

No adverse factorsn = 28 (1 progr.)

120967248240

1.0

0.8

0.6

0.4

0.2

0.0

Months

TTP

(%)

Median not reached

Median 73 months

p = 0.003

Median 23 months

8%

42%

82%

49

Smoldering myeloma: more than 1 focal lesions in MRI

Hillengass 2010 JCO

50

Markers to identify High risk SMM ?

1. Serum M component (> 30 g/L)

2. Bone Marrow plasma cells (PCs > 10%)

3. Abnormal sFLC ratio (< 1/8 or > 8)

4. Ratio abn BMPC/normal BMPC using immunophenotyping (≥ 95%)

5. Immunoparesy (Hypogammaglobulinemia = 25% decrease of normal)

6. Abnormal MRI

7. How markers change overtime…

8. All of the above?

Other Risk Factors

‐ Cytogenetics: del 17p13, t(4;14), gain 1q21, non‐hyperdiploidy by FISH–intraclonal heterogeneity by Whole Genome Sequencing–GEP70–Circulating plasma cells–clinical parameters

Walker 2013 Leukemia, Dhodapkar 2013 Blood Neben 2013 JCO

High Risk Smoldering Multiple Myeloma

Problems:– Overlap between different stratification systems not very high

– Wide variety of disease outcomes– Indication for treatment?– Early myeloma?

MM: Oncology perspective

SmolderingMM

Early intervention

Cure Chronic disease management

Agressive clonal selection

54

The 52 years old lady

Plasma cells 25%

M spike 30g/L +hypogammaglobulinemia >25%: 3g/L

sFLC kappa 550mg/L, ratio at 250

Abnormal MRI: more than 1 focal lesion, no osteolysis

55

Should we treat the High Risk SMM?QuiRedex : Len‐dex vs abstention

Lenalidomide plus Dexamethasone for High‐Risk Smoldering Multiple Myeloma

María‐Victoria Mateos, M.D., Ph.D., Miguel‐Teodoro Hernández, M.D., Pilar Giraldo, M.D., Javier de la Rubia, M.D., Felipe de Arriba, M.D., Ph.D., Lucía López Corral, M.D., Ph.D., Laura Rosiñol, M.D., Ph.D., Bruno Paiva, Ph.D., Luis Palomera, M.D., Ph.D., Joan Bargay, M.D., Albert Oriol, M.D., Felipe Prosper, M.D., Ph.D., Javier López, M.D., Ph.D., Eduardo Olavarría, M.D., Ph.D., Nuria Quintana, M.D., José‐Luis García, M.D., Joan Bladé, M.D., Ph.D., Juan‐José Lahuerta, M.D., Ph.D., and Jesús‐F. San Miguel, M.D., Ph.D.

N Engl J Med 2013; 369:438‐447

56Mateos MV, et al. Blood. 2010;116:[abstract 1935]. Updated data presented at ASH 2010.

QuiRedex : Len‐dex vs abstention

High Risk SMM

PCs BM ≥ 10% plus M‐comp ≥ 30 g/L

or

PCs BM ≥ 10% or M‐protein ≥ 30 g/L

AND BM aPC/nPC > 95% plus immunoparesy

No CRAB (hypercalcemia, anemia, bone lesions, renal impairment)

+ Time between diagnostic and inclusion in Quiredex <5 years

Lenalidomide25 mg/daily during 21d every 28 d

Dexamethasone20 mg D1-D4 and D12-D15 every 28 d

Therapeutic abstentionInduction

Nine 4-week cycles

MaintenanceLenalidomide

10 mg/daily during 21 devery month*

Therapeutic abstention

Schedule of therapy (n:126 pts)

Treatment arm(n = 57)

Control arm(n = 61)

* Low-dose Dex will be added at the moment of biological progression

Mateos MV, et al. Blood. 2010;116:[abstract 1935]. Updated data presented at ASH 2010.

Len-dex vs no treatment: TTP to active disease (n = 118)

Median follow-up: 22 months (range 5–42)

Lenalidomide + dexMedian TTP: NR6 Progressions (10%)

2 pts:early disc followed by progression 4 pts:symptomatic progressions

No treatmentMedian TTP: 25m28 Progressions (46%)

13 patients: bone disease5 patients: renal failure

HR: 6.2; 95% IC (2.6–15); p < 0.0001

454035302520151050

1.0

0.8

0.6

0.4

0.2

0.0

Time from inclusion

Len-dex: toxicity profile during induction (n:57)

G1-2 G3Anemia 9(15%) 1(2%)

Neutropenia 11(20%) 2(3.5%)Thrombocytopenia 6(11%) -

Asthenia 7(15%) 4(7%)Constipation 10(18%) -

Diarrhea 3(5.5%) 2(3.5%)Rash 10(17%) 1(2%)

Parestesias 3(5.5%) -Tremor 4(7%) -

Infection 7(12%) 2(3.5%)DVT 3(5.5%)

DVT prophylaxis with Aspirin (100mg) in 1 pt, oral anticoagulation in 1 pt with low INR levels andno px in the other one

Len toxicity profile during maintenance (n:50)

G1 G2 G3

Anemia 3(5%) 1(2%) -

Neutropenia 1(2%) 1(2%) -

Thrombocytopenia 1(2%) 1(2%) -

Asthenia 1(2%) -

Parestesias 1(2%) -

Tremor 1(2%) -

Infection 2(4%) 1(2%) 1(2%)

61

Len‐dex in « high risk SMM/Early MM »

Effective as induction and maintenance therapy

Addition of low dose dex is able to control the disease

Significant benefit in terms of TTP

Toxicity profile acceptable

There is no safety warnings at the present time

At least, a trend to a benefit in Overall Survival

Smoldering multiple myeloma requiring treatment: time for a new definition?Dispenzieri A, et al. Blood. 2013 Oct 21. [Epub ahead of print]

Until recently, no interventional study in patients with SMM showed improved overall survival with therapy as compared to observation.

A report from the PETHEMA-GEM group described both fewer myeloma related events and better overall survival among patients with high-risk SMM patients who were treated with lenalidomide and dexamethasone.

This unique study has prompted us to review current knowledge about SMM, and address the following questions:

1) are there patients currently defined as SMM, who should be treated routinely? 2) should the definitions of SMM and MM be reconsidered? 3) has the time come when not treating is more dangerous than treating; and 4) could unintended medical harm result from overzealous intervention?

Our conclusion is that those patients with the highest risk SMM--extreme bone marrow plasmacytosis, extremely abnormal serum immunoglobulin free light chain ratio, and multiple bone lesions detected only by modern imaging -- be reclassified as active MM, such that they can receive MM appropriate therapy and the paradigm of careful observation for patients with SMM can be preserved.

MRI, magnetic resonance imaging; sFLC, serum-free light chain

Which markers can be used to identifyhigh risk SMM/early MM?

Serum M component (>30 g/L) BMPCs (>10%) Abnormal sFLC ratio (<1/8 or >8) Ratio abnormal BMPC/normal BMPC

using immunophenotyping (≥95%) Immunoparesis

(hypogammaglobulinaemia = 25% decreaseof normal)

Abnormal MRI How markers change overtime… All of the above?

BMPCs(>60%) Abnormal

MRI sFLC ratio

>100

*Myeloma-related organ or tissue impairment (end-organ damage) related to plasma cell proliferative process: anaemia with 2 g/dL below the normal level or <10 g/dL, or serum calcium level >10 mg/L (0.25 mmol/L) above normal or>110 mg/dL (2.75 mmol/L), or lytic bone lesions or osteoporosis with compressive fractures, or renal insufficiency (creatinine >2 mg/dL or 173 mmol/L), [CRAB: Calcium increase, Renal impairment, Anaemia and Bone lesion] or symptomatic hyperviscosity, amyloidosis or recurrent bacterial infections (>2 episodes in 12 months);†For symptomatic MM, a minimum level of M-component or BMPC infiltration (although usually it is >10%) is not required; provided that these two features coexists with the presence of end-organ damageIMWG, International Myeloma Working Group

International Myeloma Working Group. Br J Haematol 2003;121:749–757; Kyle R, et al. Leukemia 2010;24:1121–1127

IMWG criteria for the classification of monoclonal gammopathies

Monoclonalgammopathy of uncertain significance(MGUS) SMM Symptomatic MM

Monoclonal (M)component <30 g/L serum ≥30 g/L serum Present

(serum/urine)AND AND/OR AND

Bone marrowplasma cells (BMPCs; %)

<10% ≥10% >10%†

AND AND ANDEnd-organ Damage* Absent Absent Present

Whole-genome sequencing in MM

38 MM patients: an average of 35 amino acid-changing point mutations

Confirm known mutations: KRAS, NRAS, and NFκB pathway

Mutations involved in protein translation, histone methylation and, unexpectedly,blood coagulation

No recurrent mutations

Hairy-cell leukaemia: BRAF mutations ~100%

Waldenstrom's: MYD88mutations ~ 90%

Chapman MA, et al. Nature 2011;471:467–472; Forbes SA, et al. Nucleic Acids Res 2011;39:D945–D950

Whole-genome sequencing in MM

Recurrently mutated genes include NRAS, KRAS, BRAF, DIS3 and DNAH51

While the genes containing the27 SNVs were also somatically mutated in the MMRC2 and COSMIC3

studies, no somatic SNVs were shared between these and the Mayo study4

Clonal heterogeneity argues in favour of drug combination rather than single-agent sequential therapies to eradicate dominant as well as minor clones that often emerge at relapse5

Re-emergence of a genetically diverse subclone at a later relapse may be sensitive to previous chemotherapy5

SNV, single nucleotide variant

1. Walker BA, et al. Blood 2012;120:1077–1086; 2. Chapman MA, et al. Nature 2011;471:467–472; 3. Forbes SA, et al. Nucleic AcidsRes 2011;39:D945–D950; 4. Egan JB, et al. Blood 2012;120:1060–1066; 5. Bahlis NJ, et al. Blood 2012;120:927–928

Tumour initiatingcell

Ancestral clones

Diagnosticdominant andminor clones

Treatment

Relapse

Subclones withunique nonlinearbranchingmutationsSubclones withlinearly derivedmutations

= Dominant clone

= Minor clone

A BC

Myélome Multiple : rôle de l’imagerie et nouveaux critères du diagnostic IMWG

Olivier DECAUX CHU de RENNES

Déclaration d’intérêts

|69

Au cours des 3 dernières années,avec les sociétés Pharmaceutiques suivantes

Orateur pour un laboratoire pharmaceutique : Celgene, Janssen, The Binding Site, Siemens, Sebia

Prise en charge par un laboratoire pharmaceutique de la participation à un congrès national ou international : Celgene, Janssen, LFB, Roche, The Binding Site, Siemens

Participation à un groupe d’experts: Celgene, Janssen

Fonds de recherche:The Binding Site

Fourniture de réactifs gratuits:The Binding Site, Siemens

Les nouveaux critères diagnostiques du myélome multiple (IMWG)

|70

Myélome Multiple / Critères diagnostiques(International Myeloma Working Group, 2003)

C HyperCalcémie

R Insuffisance Rénale

A Anémie

B Lésions Osseuses (Bones)

MGUS Myélome indolent (SMM)

Myélome multiple

< 30 g/l > 30 g/l Pas de valeur seuil

et ou

< 10% > 10% > 10%

- - +

HETEROGENEITE DES SMM

Kyle R et al. N Engl J Med 2007;356:2582‐2590

8 yr

Pic > 30 g/l et PM > 10%

Pic < 30 g/l et PM > 10%

Pic > 30 g/l et PM< 10%

• Peut‐on identifier des SMM à haut risque ?

• Bénéfice clinique d’un traitement précoce ?

• Nouvelles définitions du myélome multiple et du myélome indolent

• EN PRATIQUE

Les nouveaux critères diagnostiques du myélome multiple

Mayo Clinic modelRisk factors:

• M-protein ≥3 g/dL• ≥ 10% BM plasma

cells• FLC ratio <0.125 or >8

Spanish (PETHEMA) modelRisk factors:

• ≥ 95% aPC

• Hypogammaglobulinémie

655 patients

Plasmocytose médullaire ≥ 60%21 patients (3,2%)

95% progression à 2 ans

586 patients

RKL > 100 ‐ 90 patients (15%)

TTP 15 vs 55 mois

149 patients ‐ IRM corps entier23 patients (15%) > 1 lésion focale




• EN PRATIQUE


SMM à haut potentiel évolutif :– PCs BM ≥ 10% plus M‐protein ≥ 30 g/L (IgA ≥ 20 g/l, PBJ > 1g/24h)OU– PCs BM ≥ 10% ou M‐protein ≥ 30 g/L (IgA ≥ 20 g/l, PBJ > 1g/24h)+ plasmocytes médullaires anormaux > 95% + hypogammaglobulinémie

•+ Pas de critère CRAB•+ Temps entre le diagnostic et l’inclusion dans l’essai inférieur à 5 ans

Lénalidomide25 mg/j, 21/28

Dexaméthasone20 mg D1‐D4 et D12‐D15 /28j

AbstentionInduction9 cycles de 4 semaines

MaintenanceLénalidomide10 mg/j, 21/28 Tous les mois*

Abstention

Bras Traitement(n = 57)

Bras Controle(n = 61)

* Faible dose dexaméthasone ajoutée lors de la progression biologique

119 pts

Temps jusqu’à progression vers un myélome multiple

21 mois

NR

47 pts (76%)

13 pts (23%)

Groupe Revlimid24 progressions biologiques

18 patients ‐‐ Dexa 20 mg J1‐J4

3 RP11 SD4 MM

Survie globale Depuis l’inclusion




• EN PRATIQUE


• MGUS

• SMM

• SMM a haut potentiel évolutif TRAITEMENT PRECOCE

• Myélome mutiple

IMWG considère qu’un facteur pronostique permettant d’identifier des

SMM avec ~80% de risque de progression à 2 ans (médiane de transformation maligne à 12 mois)

permet de justifier une intervention thérapeutique précoce

Nouveaux critères diagnostiques de myélome multiple

|92

Plasmocytose médullaire clonale > 10% ou plasmocytome prouvé histologiquement

Présence d’au moins un des critères suivants - hypercalcémie (> 0,25 mmol/L /N ou > 2,75 mmol/L)

- insuffisance rénale (créat. > 177 mmol/L ou Cl créat < 40 ml/min)

- anémie (Hb < 2 g/dL / N ou < 10g/dL)

- ≥ 1 lésion ostéolytique – radiographies, TDM, TEP

- Plasmocytose médullaire clonale ≥ 60%- Rapport κ/λ ou λ/κ > 100 (et concentrtaion ≥ 100 mg/l)- > 1 lésions focales IRM (≥ 5 mm)

CRAB

NOUVE

AUX

CRITER

ES

COMPOSANT MONOCLONAL SERIQUE OU URINAIRE ?

N’EST PLUS UN CRITERE DIAGNOSTIC

MYELOME SECRETANT VS NON SECRETANT

RADIO TDM FAIBLE DOSETEP

IMAGERIE

• ≥ 1 lésion ostéolytique (≥5 mm) TDM ou TEP suffit à poser le dg de myélome

• une lésion hypermétabolique TEP sans ostéolyse sous‐jacente ne suffit pas

• si lésion focale IRM < 5 mm il est recommandé de compléter par TDM ou TEP

Nouveaux critères diagnostiques de myélome indolent

|94

IgG ou IgA monoclonale ≥ 30 g/l

ou protéine monoclonale urinaire ≥ 500 mg/24h

ou plasmocytose médullaire clonale 10-60%

Absence de critères de myélome multiple (CRAB / nouveaux critères)




• EN PRATIQUE


• MGUS

• SMM

• SMM a haut potentiel évolutif Early Myeloma

• Myélome multiple


Prise en charge des SMM nouvelle définition?

MYELOME MULTIPLE

Traitement

• Que devient le risque évolutif des SMM nouvelle définition?

• Faut‐il répéter le dosage des chaînes légères libres sériques au cours du suivi ?

• Faut‐il prévoir des IRM systématique au cours du suivi ?

• Nouveaux facteurs pronostiques ? • Critères d’évolutivité biologique et/ou IRM ?

• Essais thérapeutiques?

Prise en charge des SMM nouvelle définition?

?

Imagerie du myélome au diagnostic

|99

Cas clinique 1

Une patiente de 70 ans vous est adressée en consultation pour découverte fortuite d’une gammapathie monoclonale Ig G kappa. Le bilan biologique a été prescrit dans le cadre d’un syndrome grippal.

La patiente n’émet aucune plainte

Examen clinique normal Hb 12 g/dl, plaq 350 000/mm3, GB 6 700/mm3 (PNN 3 450/mm3)

Créatinine 78 µmol/L, urée 6 mmol/L

Calcémie 2,4 mmol/L

Pic estimé à 35 g/l

Protéinurie 0,1 g/24 h (PBJ +)

Myélogramme : plasmocytose médullaire 20%

|100

Quel examen d’imagerie prescrivez vous?

Radiographies osseuses

Scanner osseux corps entier (faibles doses)

IRM pelvi-rachidienne

IRM corps entier

TEP-scanner

Aucun examen d’imagerie n’est nécessaire

|101

Vous avez prescrit un scanner osseux qui n’objective pas de lésions lytiques osseuses. Comment compléter vous le bilan d’imagerie?


IRM corps entier

TEP-scanner

Aucun examen d’imagerie supplémentaire n’est nécessaire

|102

L’IRM objective une lésion focale de 5 mm de l’aile iliaque droite. Après discussion en RCP il est proposé une surveillance clinique et biologique à 6 mois. Si l’évolution clinique et biologique est stable, un contrôle de l’IRM au cours du suivi vous parait-il pertinent ?

OUI

NON

|103

• 63 SMM • ≥ 2 IRM au cours du suivi

Progression IRM

Stabilité IRM

Cas clinique 2

Une patient de 55 ans vous est adressé en consultation pour découverte d’une gammapathie monoclonale Ig A kappa dans un contexte d’asthénie,

Le patient se plaint d’une asthénie et d’une dyspnée d’effort stade II

Hb 8 g/dl, plaq 150 000/mm3, GB 6 700/mm3 (PNN 3 450/mm3)





Myélogramme : plasmocytose médullaire 25%

|107

Quel examen d’imagerie prescrivez vous ?




IRM corps entier

TEP-scanner


|108

Vous avez prescrit des radiographies osseuses qui n’objectivent pas de lésions lytiques osseuses. Comment compléter vous le bilan d’imagerie?


IRM corps entier

TEP-scanner


|109

Vous avez prescrit un scanner osseux qui objective plusieurs lésions lytiques du rachis et du bassin. Aucune lésion ne semble menaçante. Comment compléter vous le bilan d’imagerie?


IRM corps entier

TEP-scanner


|110

Cas clinique 3

Une patiente de 75 ans est hospitalisé pour douleurs dorsales révélatrice d’un d’une lésion lytique de T12. La biospie de T12 conclut au diagnostic de plasmocytome osseux.

Hb 12 g/dl, plaq 350 000/mm3, GB 6 700/mm3 (PNN 3 450/mm3)





Myélogramme et BOM : plasmocytose médullaire 2-3%

|111

Quel examen d’imagerie prescrivez vous?




IRM corps entier

TEP-scanner


|112

Vous avez prescrit un scanner osseux qui n’objective pas d’autres lésions lytiques osseuses. Comment compléter vous le bilan d’imagerie?


IRM corps entier

TEP-scanner


|113

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