International Myeloma FoundationInternational Myeloma FoundationPatient and Family SeminarPatient and Family Seminar

May 5th, 2006

Vienna, Austria

Myeloma for Beginners

Brian G.M. Durie, M.D., ChairmanInternational Myeloma Foundation

Main Features of Myeloma

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Incidence of Multiple Myeloma Around the World

Asia 1-2/100,000West 5-10/100,000

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STRESS FACTORS

Four Major Factors

VIRUSES

RADIATION

CHEMICALS

e.g. IL-6

MYELOMA CELL

DNA DAMAGE

Microenvironment

Causes of Myeloma

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Development of Monoclonal Myeloma

Build up of DNA damagedplasma cells: Myeloma monoclonal population

Plasma Cells

Trigger Factor(s)

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How Patients Present 2006

BONE ISSUES 30%ROUTINE PHYSICAL 25%*ELEVATED urine/serum protein 15%ANEMIA/FATIGUE 15%INFECTION 3%RENAL DYSFUNCTION 2%MISCELLANEOUS 10%

* IMF: Myeloma Interactive 2003/2004/2005/2006

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Initial Testing

BloodComplete blood countsChemistry profileSß2м; AlbuminCRP; LDHSPEP: IFE/IEPQuant. Immunoglobulins

UrineUPEP on 24 hr urine

Bone marrow asp/biopsyX-rays

Skeletal survey

* MRI; PET; CT/PET

* Serum FREELITE

* Cytogenetics/FISH

* Molecular testing: GEP; SNPs; proteomics; RNA/DNA sequencing

Standard Tests Selective Testing

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SPEP/ UPEP and ImmunofixationEssential Data to Track Response

SPEP

UPEP

Serum Immunofixation

Urine Immunofixation

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New Clinical Criteria for Myeloma**

Very Much Dependent Upon Bone Disease Documentation

MGUS PC < 10%; SPIKE < 3.0G/DLSmoldering not MGUS or MM; D/S stage IAMyeloma (MM*) “End Organ Dysfunction,” i.e. 1 or more of:

Calcium elevation (> 10.5G/DL)Renal insufficiency (CREAT > 2mg/DL)Anemia (HB < 10 or 2G < Normal)Bone disease (Lytic or Osteopenic)

*MM is same as Durie/Salmon stage IB plus stage II/III A/B** British J. Haemat. 2003; 121: 749-757

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Assessment of Bones Essential

X-ray: full skeletal surveyCT scan or MRI with gadolinium enhancementWhole body FDG/PET or CT-PETBone densityBone molecular studies, e.g. urinary NTX

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Bone Damage

NORMAL DAMAGED TRABECULAE

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Prognostic Factors for Staging

International Staging System International Staging System ββ22M / S. AlbM / S. Alb

Stage IMedian: 6 years

Low β2M < 3.5* plusS. Albumin** > 3.5 G/DL

Stage IIMedian: 4 years

β2M < 3.5 but low albumin < 3.5 orβ2M : 3.5 – < 5.5

Stage IIIMedian: 2 years

High β2M > 5.5mg/DL

Based upon 10-15 years follow-up* mg/DL** Gm/DL

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International Staging System

Overall Survival by ISSAsia

0%

20%

40%

60%

80%

100%

0 24 48 72 96 120 144 168 192 216Months from initial chemo treatment

ISS Stage IISS Stage IIISS Stage III

Deaths / N131 / 255159 / 240181 / 246

Medianin Months58 (47,64)38 (31,42)24 (19,30)

Overall Survival by ISSEurope

0%

20%

40%

60%

80%

100%

0 24 48 72 96 120 144 168 192 216Months from initial chemo treatment

ISS Stage IISS Stage IIISS Stage III

Deaths / N539 / 1305912 / 1771894 / 1425

Medianin Months71 (65,75)52 (49,55)32 (30,36)

Overall Survival by ISSNorth America

0%

20%

40%

60%

80%

100%

0 24 48 72 96 120 144 168 192 216Months from initial chemo treatment

ISS Stage IISS Stage IIISS Stage III

Deaths / N591 / 747

1012 / 1146943 / 1022

Medianin Months55 (51,60)40 (37,42)26 (24,29)

Asia

Europe North America

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Tracking Test ResultsB2M/ AlbuminType of “M-spike”; blood/ urineAmount of “M-spike”Chromosome 13; [4;14]; otherBone damage or notKidney damage or notDental evaluationMonitor all routine testsTrack M-spikeFollow-up x-rays/ scansRecheck kidney status; creatinine

Baseline

Follow-up

Other

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Serum Free Light Chain Assay

Advantages for MonitoringAdvantages for Monitoring

Allows non-secretory patients to enter trialsCan reduce use of 24-hr urine testingEnables monitoring of patients with normal SPEP or IFEResponse detected earlier than with other assays• Can supplement MRI

Clear Recommendations Required

Mutual Agreement is Very Helpful

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Mental Health

Reduce stressHave confidence in the treatment planExpect remissionSet future plansDevelop realistic HOPE

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To Reduce Stress, Make Changes

Slow down & plan.

Life can be too fast…

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Work with Your Doctor

Keep her/ him informed Enlist cooperationOpenly discuss questions/ concernsSeek the best care feasible

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Take Care of Yourself

ResveratrolKill Myeloma Cells

Promote Healing

Enhance Relaxation

Help Others When You Can

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