MYELODYSPLASTIC SYNDROME PROGNOSIS TREATMENT OPTIONS JILL FULCHER MD

MYELODYSPLASTIC SYNDROME: PROGNOSIS & TREATMENT OPTIONS JILL FULCHER MD Ph. D FRCP(UK) 13 TH OCT 2018 www. ottawahospital. on. ca | Affiliated with • Affilié à

NORMAL BLOOD SMEAR 1. Red cells - Contain Hb - Anemia when low 2. White cells - neutrophils - Infection when low 3. Platelets - Clot formation - Bleeding when low 2

NORMAL HEMATOPOIESIS ▶ Blood cells are made in the bone marrow ▶ Hematopoietic stem cell (HSC) ▶ Undergo a series of developmental steps resulting in mature red cells, neutrophils and platelets ▶ Released into bloodstream 3

MYELODYSPLASTIC SYNDROME Chung SS & Park YP. 2017. Blood Advances; 1(26): 2572 -8 Affiliated with • Affilié à 4

MDS: ABNORMAL HAEMATOPOIESIS Normal Myelodysplastic Syndrome Anemia, infection, bleeding Affiliated with • Affilié à 5

Prognostic Scoring System for MDS Affiliated with • Affilié à 6

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Steensma Blood Cancer Journal (2018) 8: 47 Affiliated with • Affilié à 8

Medications: SYMPTOMATIC MDS - Tranexamic acid Antibiotics Antiviral agent Anti-fungal agent (TPO receptor agonists) • bleeding • Infections • fatigue, SOB +/- Iron chelation 9

ANEMIA – Trial of Erythropoietin Replacement Therapy (ERT) ▶ Response rate predicted from: • Serum EPO level • Transfusion requirements • 74% chance of responding when EPO < 500 U/L, <2 units RBC/mth • 7% if EPO > 500, >2 units RBC/mth ▶ Target Hb 100 -120 g/L ▶ Synergy with GCSF 10

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OTHERAPIES FOR LOWER-RISK MDS ▶ Lenalidomide ▶ Immunosuppressive therapy (IST) ▶ Immuno-modulating agent ▶ ATG + cyclosporine ▶ MDS with del(5 q) with anemia ▶ More likely to work in patients: • 10 mg/d for 21 d out of 28 d • 60 y/o or younger • Response in 4 -6 weeks • Low-risk disease • Rise in Hb of 32 g/L • BM blasts < 5% • 65 - 70% achieve transfusion independence, 30 -40% cytogenetic remission • Bone marrow hypoplasia • Improves survival (2 y OS 90%v 74%) • S/E: low neutrophils, low platelets, rash, GI, ? secondary malignancy • Normal cytogenetics • HLA-DR 15 • PNH clone 12

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The only cure for MDS is Hematopoietic Stem Cell Transplantation Affiliated with • Affilié à 14

Myelodysplastic Syndrome: a disease mostly of the elderly • Mean age at diagnosis 70 -75 y • Incidence : 4. 9 per 100, 000/year • <40 y 0. 1 per 100, 000/year • 70 -79 y 30. 2 per 100, 000/year • >80 y 59. 9 per 100, 000/year Buckstein R. Leuk Res 2009; 33: 1313 -8 Williamson PJ, et al. Br J Haematol. 1994; 87: 743 15

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CO-MORBIDITIES AFFECT TRANSPLANT OUTCOMES Sorror et al, 2005. Blood; 106(5): 2912 -2919 17

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HYPOMETHYLATING AGENTS Affiliated with • Affilié à 19

Fenaux et al, Lancet Oncol 2009 Effect of Azacitidine in Higher-risk MDS (>/= IPSS-2) • 358 patients • Median OS: vs 15 mths 24. 5 • Alive at 2 years: 51% vs. 26% • Transformation to AML: 11. 5 vs. 17. 8% 20

AGENTS IN CLINICAL TRIAL ▶ Hypomethylating agents (HMAs) ▶ • Decitabine iv Erythroid Stimulating Agents • Luspatercept • Guadecitabine (SGI-110) • Oral azacitidine (CC 486) • Oral decitabine (Cedurazine) ▶ Thrombopoiesis Stimulating Agents • TPO mimetics - Romiplostin (intectable) - Eltrombopag (oral) 21

Timing of Transplant in Lower-risk MDS De Witte et al. 2017. Blood; 127(13): 1753 -1762 22

THANK YOU QUESTIONS? 23