Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic...
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Transcript of Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic...
![Page 1: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/1.jpg)
Current Treatment Options in MDSDick Wells MD, DPhil, FRCPCDirector, Crashley Myelodysplastic Syndrome Research LaboratoryOdette Cancer Centre
![Page 2: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/2.jpg)
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?
![Page 3: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/3.jpg)
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
![Page 4: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/4.jpg)
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
![Page 5: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/5.jpg)
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
![Page 6: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/6.jpg)
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
![Page 7: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/7.jpg)
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
![Page 8: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/8.jpg)
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![Page 9: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/9.jpg)
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?
![Page 10: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/10.jpg)
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
![Page 11: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/11.jpg)
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
![Page 12: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/12.jpg)
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
![Page 13: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/13.jpg)
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
![Page 14: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/14.jpg)
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Response to immune suppression
![Page 15: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/15.jpg)
Immune suppression in MDS
Upside• Durable responses• Can improve all
blood counts
Downside• Expensive• Very toxic
(especially ATG)• Not everyone
responds
![Page 16: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/16.jpg)
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
![Page 17: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/17.jpg)
• 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…
![Page 18: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/18.jpg)
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
![Page 19: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/19.jpg)
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Neutrophils
![Page 21: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/21.jpg)
“Doc, I’m a new man!”
0
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![Page 22: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/22.jpg)
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
![Page 23: Current Treatment Options in MDS Dick Wells MD, DPhil, FRCPC Director, Crashley Myelodysplastic Syndrome Research Laboratory Odette Cancer Centre.](https://reader035.fdocuments.in/reader035/viewer/2022062712/56649c945503460f94950313/html5/thumbnails/23.jpg)
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