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Multiple myeloma:

Diagnosis & Management

Rakesh PopatUCL Cancer Institute & University College London Hospitals

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Bone marrow

Bone Kidney

Blood cell production

How does myeloma affect the

body?

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Clinical Features

Kidney dysfunction (70%)

Recurrent infections

Bone marrow failure

(anaemia)

Hyperviscosity

Bone pain (70%)

High calcium levels

Pathological fractures

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Diagnostic Investigations

Blood urine Bone marrow biopsy Skeletal survey

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Is treatment required?

Normal MGUS Asymptomatic

myeloma

Myeloma

No bone lesions

> 10% plasma

cells

SymptomsBone painAnaemiaKidney failure

No bone lesions

< 10% plasma

cells

NO TREATMENT REQUIRED

OBSERVATION ONLY

TREATMENT

REQUIRED

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How myeloma may affect your patient?

Everyones myeloma is different - it is a veryindividual disease

Complex and debilitating disease to live withwhich affects patients not only physically butalso: Emotionally: scared, angry, confused, but also relief

after proper diagnosis, accepting of challenges ahead Socially: Relationship with family and friends, ability to

work, financial impact

Also has a huge impact on the family

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Diagnosis if myeloma is active

Relapse after previous treatment(s)

Refractory to previous treatment(s)

When is treatment considered ?

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Disease course now more characteristic of a chronic condition

Less distinction between different stages because of:

- Improved characterisation of myeloma genetics

- better diagnostic tools

- more treatment options

- more flexible treatment schedules

- consolidation treatment and maintenance treatment

Current thinking

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Types of treatment

Myeloma-directed treatment Supportive treatment

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Treatment tool-kit

Most effective approach is a combination of treatments

Anti-myelomatreatment

Support& Care

Bisphosphonates

Others:

Surgery

RTY

Pain relief

TransfusionAntibiotics

Dialysis

Emotional

support

Home help

Social support

Carers

support

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Consultant haematologist, registrar Clinical Nurse Specialist Radiologist Physiotherapist Palliative care team Dietician Counsellor/social worker

Patients now have a role and/or say in their

healthcare promote an alliance with your patients

Myeloma MDT

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Control myeloma

Achieve maximum response with the minimum of side-effects

Slow disease progression and aim for longest possible

remission / plateau

Relieve pain and address other symptoms

Prevent further damage to the body

Improve and preserve quality of life for as long as possible

Treatment aims

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Treatment decisions: medical perspective

TreatmentRecommendation

Localissues:

Capacity

Funding

Experiance

Patientneeds &

priorities

Evidence &Guidelines

PriorTreatment

&Response

PatientFeatures

DiseaseFeatures

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Dise

ase&Progn

osis How does the

myeloma effectme?

Whats my goal,what do I want?

How will I expectto feel?

Tr

eatmentOpt

ions What are my

options?

What are theside-effects

What should Iexpect?

How long doestreatment last?

Practicalities Do I have to

stay in hospital?

Can I still work? How far do I

have to travel &what time?

Can you helpwith money?

Treatment decisions: the patients perspective

Consent to treatment should be an informed one

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IntensiveYoungerGenerally fitAutologous

stem cell transplant

Non-intensiveOlderOther medical

problemsChemotherapy

Treatment Options

Important to discuss options

Treatment is specific for theindividual

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Approach to Treatment

Thalidomide

(Velcade) Velcade Revlimid

Clinical

Trial

Option

Clinical

Trial

Option

Clinical

Trial

Option

Clinical

Trial

Option

?

Autologous

Stem cell

Transplant

Autologous

Stem cell

Transplant

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2. Stem cell mobilisation

3. Stem cell collection

4. High dose melphalan

1. Induction

chemotherapy 5. Autologousstem cell transplant

Aim is to improve the chance of complete remission

Standard intensive treatment

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Standard non-intensive

treatments

Thalidomide

Velca

de

Supportive

All combinations are effective and generally well tolerated

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Response to treatment

Stable

Disease

100%

Partial Response

50%

Very Good

Partial Response

10%

Complete

Response

0%

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Current approved treatment at first relapse: VELCADE

Despite effective initial treatment, the myeloma eventuallyprogresses in all patients.

Relapse: Increase of paraprotein by 25% or more from baseline

- treatment is required if there is a return of symptoms

First relapse

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First type of proteasome inhibitor used to treat myeloma.

Also known as bortezomib

Proteasomes act as a recycling mechanism for cells

Velcade blocks the proteasome results in cell death

Protein Tagged for

recycling

Proteasome

Amino acids and

protein fragments

Velcade

Velcade

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Results from clinical studies show approximately 30%of relapsed patients respond to Velcade alone, 50% to

Velcade/dex and > 80% to Velcade and other combinations

Responses last for ~ 12 18 months

Responses are seen in patients even in heavily pre-treated

patients, including transplant

Can be used in patients with kidney failure

Mostly predictable side-effects peripheral neuropathy

Generally given with dexamethasone cyclophosphamide

Velcade

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Multiple relapse is inevitable in myeloma. Need to thinknot only about immediate needs but also consider what

you want in the future keep options as open as

possible

Other options:

1. Consider same initial treatment if lengthy first remission

2. Thalidomide combination if not previously received it

3. Second transplant if remission > 18 months

4. Consider entering a clinical study

Other options at first relapse

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Current approved treatment at second relapse is REVLIMID

Immunomodulatory drug with multiple mechanisms of action

Structurally related but chemically distinct from thalidomide

Blocks chemical

signals required formyeloma cell growth

Boosts immune system

Directly kills myeloma cells

Blocks growth of new blood vessels

Second relapse

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Taken orally

High rate of complete responses: 30 - 40% as monotherapy; 50 -

60% with dex; 70 90% with other combinations.

Good duration of response ~ 18 24 months

Lower incidence of common thalidomide side-effects i.e. less

peripheral neuropathy, DVT, constipation etc

Can be effectively and safely combined with other treatments

including chemotherapy and steroids

Approved for use in combination with dex, continue treatment until

disease progression

Revlimid

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Options:

Consider previous treatments that have given lengthy

remission

Enter clinical trialOther strategies such as DTPACE or ESHAP Non-approved drugs via access schemes

Subsequent relapse

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Clinical Trials: New Drugs

Survival

Myelomacell

Healthy bone marrow cells

H

H

H

H

H

X

X

X X

X Immune cells

X

Myeloma

Cell

Supporting cells

XProteasome

DNA

Heat Shock

Proteins

Cytokines

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Clinical Trial Drugs

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An approach to treatment

Thalidomide Velcade RevlimidClinical

Trials

Clinical

Trials

Clinical

Trials

Disease assessments

Treatment Palette

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Myeloma is an individual disease and requires a personalisedapproach

It is important that patients have a role in their treatment plan

Patients should discuss their goals and perceptions to those

caring for them

Treatments and access to them have greatly improved

But, remains a difficult and challenging disease

Lots more research required to understand and develop

better treatments

Summary