low risk myelodysplastic syndromes (mds)
TRANSCRIPT
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Low Risk Myelodysplastic Syndromes (MDS)
Tiffany Tanaka, MDUC San Diego Moores Cancer Center
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Diagnosis
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Bone Marrow Biopsy
cancer.gov (National Cancer Institute website)
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Bejar, Curr Hematol Malig Rep 2015
Diagnoses that look like MDS (but aren’t!)
Tanaka, Bejar, Blood 2019
Benign Causes Non-Benign (“Clonal”) Causes
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How MDS affects patients• Low blood counts• Increased bleeding, infection, anemia• One-third of patients develop acute myeloid leukemia (AML)
DNA Changes (mutations)
90% of patients
Changes in Cell Shape
Cazzola et al, Blood 2013
Chromosome Changes
50% of patients
ASH Image Bank –James Vardiman
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MDS subtypes (based on bone marrow)
Arber et al, Blood 2016
MDS patients have “dysplasia” in greater than 10% of bone marrow cells, and less than 20% blasts (leukemia cells)
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What is my MDS stage?International Prognostic Scoring System, Revised (IPSS-R)
1. HemoglobinRed Blood Cells
2. Absolute Neutrophil CountType of White Blood Cell
3. Platelet CountClotting Cells
4. Bone Marrow BlastsLeukemia Cells
5. Chromosome Abnormalities
• Very Low Risk
• Low Risk
• Intermediate Risk
• High Risk
• Very High Risk
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https://www.mds-foundation.org/ipss-r-calculator/
IPSS-R CalculatorExample Patient
Margie is a 78-year-old woman with:
Hemoglobin 8.2 g/dL
Neutrophils 2.3 x 109/L
Platelet 240 x 109/L
Bone marrow biopsy shows: Blasts 1%Chromosomes Normal
The lower the score, the better!
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Lower Risk = Better Survival
Bejar et al. Haematologica 2014; Greenberg et al. Blood 2012
VERY LOW
LOW
INTERMEDIATE
HIGH
VERY HIGH
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Genetic Variation of MDS
Bejar et al, N Engl J Med 2011
Haferlach et al, Leukemia 2014Papaemmanuil et al, Blood 2013
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Gene mutations may aid the diagnosis of MDS, and may also predict survival
NCCN Guidelines –MDS
Genes Mutations in MDS
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Treatment
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General Approach
Platzbecker et al, Blood 2019
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Treatments for Low Risk MDS
• Close Monitoring
• Supportive Treatment: Blood transfusions, Iron chelation
• Erythropoiesis stimulating agents (ESA)
• Lenalidomide for del(5q)
• Luspatercept for MDS-RS Subtype
• Hypomethylating Agents (Azacitidine, Decitabine) might be considered
• Immunosuppressive Therapy (ATG, Cyclosporine) in select situations
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Treating Anemia
Anemia Only
Mild Observe
Moderate/Severe
No Del(5q), Check Epo Level
Less than 500: Epo (ESA)
If no improvement, Luspatercept
500 or more:Luspatercept
Del(5q) Only Lenalidomide
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Erythropoiesis-Stimulating Agents (ESA)• Epoetin Alfa or
Darbepoietin
• Stimulate red blood cell production
• Subcutaneous injections every 1-2 weeks
• Side effects: headache, joint pain, high blood pressure, thrombosis (rare)
Fenaux et al. Leukemia 2018
Patients with Epo level below 200 have better responses that last longer
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List et al. N Engl J Med 2006ASH Image Bank –James Vardiman
Lenalidomide• Lower-risk MDS with del(5q)
• Oral (pill)
• 70% of patients no longer require transfusions
• 50% of patients experience “cytogenetic response,” where the del(5q) abnormality is no longer found
• Side effects: Low blood counts, nausea, diarrhea, fatigue, itching
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• Lower-risk MDS with ring sideroblasts (MDS-RS)
• No response to ESA or Epo level above 500
• Subcutaneous injection every 3 weeks
• 38% of patients no longer required transfusions after 6 months
• Side effects: Low back pain, fatigue, nausea, diarrhea, dizziness
Fenaux et al. N Engl J Med 2020Acceleron Pharma
Luspatercept
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More than anemia?
Thrombocytopenia, Neutropenia, or
Bone marrow blasts
Supportive Treatments
Hypomethylating Agents
(Azacitidine, Decitabine)
If favorable response, continue until progression
No response:Clinical trial or bone marrow transplant
Immunosuppressive Therapy
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Hypomethylating (HMA) Therapy• Azacitidine, Decitabine• IV, SQ (*oral decitabine-cedazuridine)• Blood counts initially worsen, more
transfusions needed• Slow responses in most (4-6 months)• Treatment schedule
- Azacitidine day 1-7, every 28 days- Decitabine day 1-5, every 28 days
• Side effects: nausea, constipation, worsened blood counts
Fenaux et al. Lancet Oncol 2009
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HMA Responder
Hgb
Plt
WBC
HMA Non-Responder
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THANK YOU!
UCSD ACTRI KL2: 1KL2TR001444UCSD BMT & Hematology Clinical TeamsRafael Bejar MD PhDSoo Park MD
UCSD Research TeamRandy TsaiXinlian Zhang PhDBrian Reilly PhDDinh Diep PhD
OUR PATIENTS!
AAMDS International FoundationNeil HorikoshiAlice Houk and Leigh Clark