Current Treatment Options in MDSDick Wells MD, DPhil, FRCPCDirector, Crashley Myelodysplastic Syndrome Research LaboratoryOdette Cancer Centre

Tale of Two Patients

Mr. Blue• Low Hb, WBC, platelets

• >90% chance of developing leukaemia within 2 years

• Life expectancy about 18 months

Ms. Green• Anaemia only

• ~10% chance of developing leukaemia ever

• Life expectancy more than 10 years

They both have MDS, but do they both have the same disease?

MDS is at least two diseases

• Some patients (“high risk”) have a severe disease that rapidly evolves into acute leukaemia

• Others (“low risk”) have a chronic disease that makes them anaemic

Different situations, different goals

Low Risk MDS

To alleviate anaemia and to minimize the harm

caused by transfusion

High Risk MDS

To prevent the development of

leukaemia and to extend lifespan

Treatment Options for High Risk MDS-prevent leukaemia, extend lifespan

• Supportive/palliative care

• Allogeneic bone marrow transplantation– Donor not always available– High risk, high relapse rate

Is that all there is?Other options for high risk MDS

Hypomethylating drugs

• Vidaza (Pharmion)

• Dacogen (MGI Pharma)

What they do: “Rehabilitate” bone marrow cells in MDS by changing their pattern of gene expression

Hypomethylating drugs:Clinical trials

• Vidaza and Dacogen beat supportive care – Major responses in 20-25%– Responders remained or became transfusion

independent and symptoms improved– Duration of response <1year

• Delayed time to AML progression or death

• Trend toward improved survival

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Hypomethylating drugs for MDS

Upside• Improve counts• Delay leukaemia• May improve

survival• Improve quality of

life

Downside• NOT AVAILABLE!• Expensive• Not everyone responds• Temporary responses• Best duration of

treatment unknown– Forever?

Treatment Options for Low Risk MDS-alleviate anaemia, reduce transfusion harm

• Transfusion– 90% of patients – Iron chelation

• To remove excess iron due to transfusion

• “Growth factors”– To boost red blood cell production

• Immune suppression– To protect developing blood cells

Epo and Red Blood Cells

• Red blood cells carry oxygen

• If not enough oxygen gets to the kidney, epo is released

• Epo tells the bone marrow to make more red blood cells

Giving extra epo can help boost haemoglobin in MDS

Growth factors for MDS

Upside• Easy• Not toxic• Can get transfusion

independence

Downside• Expensive• Needles!• Not everyone responds• Temporary responses• No effect on platelets or

WBC

Immune Suppression

• The theory:– In MDS, as in aplastic anaemia, the

immune system attacks the bone marrow. Drugs that block the immune system may help.

• The evidence:– About 50% of MDS patients respond to this

sort of treatment

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Immune suppression in MDS

Upside• Durable responses• Can improve all

blood counts

Downside• Expensive• Very toxic

(especially ATG)• Not everyone

responds

Is that all there is?Other options for low risk MDS

Revlimid• “Cousin” of thalidomide• Many biological activities• Early studies: amazingly active in patients

with MDS and chromosome 5 abnormalities

• Most frequent chromosomal deletion in MDS patients– 10-20% (+/- other

abnormalities)– 5-6% as sole abnormality

• Better-than-average prognosis– Low risk of leukaemia

Deletion 5q [del(5q)]A problem with the long arm…

MDS-003 trialRevlimid in 5q- MDS

• 67% of patients achieved transfusion independence

• 90% of patients who achieved a transfusion benefit did so by completion of 3 months of therapy

• Durable responses (>2 y)

67% Transfusion

Independence(99/148 patients)

List et al., N Eng J Med, 355, 1456, 2006

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Neutrophils

“Doc, I’m a new man!”

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Revlimid in MDS

Upside• Amazingly active in 5q-

MDS• Oral, once daily• Pretty easy to take• Currently available on

SAP; Health Canada approval around the end of 2007

Downside• Lowers WBC and

platelet counts (initially)• Expensive!• Restricted to low risk

5q- MDS

Summary:Algorithms for MDS

1. If 5q-, revlimid

2. If epo<500, try growth factors

3. Immune suppressive therapy (ATG and/or cyclosporine)

1. If feasible, BMT

2. Supportive/palliative care

3. …or clinical trial

4. … or hypomethylating drugs