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Advances in the Management of Myelodysplastic Syndromes
Allen S. Yang, MD. Ph.D.Jane Anne Nohl Division of HematologyNorris Comprehensive Cancer Center
University of Southern California
Southwestern Conference on Medicine
May 1, 2009
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Disclosures:
Celgene, Eisai, Bristol Myers SquibbMethylgene, NovartisTherEpi
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CASE 1
60 year old retired high school chemistry tearcher. Presents with a 3 month history of feeling “tired”.
WBC: 12.0Hgb/Hct: 8.8/24.0Plt: 191
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CASE 1
What intervention would you recommend next?
A) ColonoscopyB) Bone Marrow biopsyC) Review of Peripheral SmearD) A trial of iron replacement
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CASE 2
76 year old retired oil worker with a past medical history of NHL (non-Hodgkin’s lymphoma) cured with CHOP chemotherapy. Patient has a routine CBC as part of an annual physical exam.
WBC: 12.0Hgb/Hct: 8.8/24.0MCV: 95Plt: 56
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CASE 2
What intervention would you recommend next?
A) ColonoscopyB) Bone Marrow biopsyC) Review of Peripheral SmearD) A trial of iron replacement
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Causes of anemia in elderly
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Anemia* in the Elderly (Age ≥ 65 Years)
*Anemia was defined as < 13 g Hgb/dL for men and < 12 g Hgb/dL for women.Percentage of persons age 65 and older who are anemic. Source: NHANES III, Phases I and II, 1988–1994.Adapted from Guralnik et al. Hematology. 2005;528-532, with permission.
0
5
10
15
20
Total Population ≥ 65 Y
Perc
enta
ge o
f Per
sons
MalesFemalesTotal
11.010.2 10.6
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Anemia in the Elderly (Age ≥ 65 Years) (cont)
34Unexplained
32Chronic illness/inflammation or chronic renal failure
34Blood loss/nutrition relatedPercentageType of Anemia
• Unrecognized MDS may represent an important cause of unexplained anemia in the elderly
Guralnik et al. Hematology. 2005;528-532.
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What is MDS?
Other names:- Refractory anemia (1938)- Preleukemia (1953)- Smoldering leukemia (1963)- Dysmyelopoietic anemia (1980)- MDS (1982)
Clonal? Heterogeneous? Myeloid?
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The Myelodysplastic SyndromesEpidemiology
• 15,000 new cases/year in US (Adults)
• More common than AML
• Median Survival 1-3 years
• Predominantly a disease of the elderly– Median age > 60– Greater incidence in males than females– Incidence increases with age
Kurzrock R. Semin Hematol. 2002 Jul;39(3 Suppl 2):18-25.Steensma DP, Tefferi A. Leuk Res. 2003 Feb;27(2):95-120..Bennett JM, et al. Bennett JM, et al. Int Int J J HematolHematol. 2002 Aug;76 . 2002 Aug;76 Suppl Suppl 2:2282:228--38.38.
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Etiology of MDS
• benzene or toluene
• gasoline or diesel (?)
• pesticides (?)
• virus (?)
• genetic (?)
• secondary to chemotherapy with or without radiation therapy
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Probability of Treatment-related MDS (tMDS) After Autologous
Transplantation for NHL
Friedberg JW, et al. J Clin Oncol. 1999;17(10):3128-35.
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Differential Diagnosis of MDS
• nutritional deficiencies
• heavy metal poisoning
• alcoholism
• metabolic disturbances
• chronic inflammation
• Tuberculosis
• liver disorders
• hypersplenism
• Hodgkin’s disease
• metastatic carcinoma
• recent chemotherapy
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The Myelodysplastic SyndromesOverview
• Clonal disorder characterized by hypercellular marrows, peripheral cytopenias, and cell functional abnormalities
• Dominant feature: Ineffective hematopoiesis with peripheral blood cytopenias
• Bone marrow failure– Majority succumb to infection or bleeding– Transformation to acute leukemia in 35-40% range
• High mortality rate
• Supportive Care has been the standard treatment
Kurzrock R. Semin Hematol. 2002 Jul;39(3 Suppl 2):18-25.Miller KB. Curr Treat Options Oncol. 2000 Apr;1(1):63-9.
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Clinical Presentation
• Half of patients are >70 years old
• Half of patients have no symptoms related to MDS
• Most common symptoms are those from anemia
• A few patients have symptoms of bleeding or infection
• Physical findings are unusual; splenomegaly found in <20%
• Some patients present with fever
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Age-Related Incidence of MDS
0 0 2 1 2 2 49
16
26
5259 61
34
10
10
10
20
30
40
50
60
70
20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80- 85- 90- 95-
Williamson PJ, et al. Br J Haematol. 1994;87:743-745.
Age in 5-Year Blocks
Age-Specific Incidence Rates (per 100,000), Years
<50 0.550-59 5.360-69 1570-79 4980 and over 89
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MDS FAB Classification
8-60+1%-20%CMML(Chronic Myelomonocytic Leukemia)
5-1221%-30%RAEB-T(Refractory Anemia with Excessive Blasts in transformation)
7-155%-20%RAEB(Refractory Anemia with Excessive Blasts)
21-76<5%RARS(Refractory Anemia with Ringed Sideroblasts)
19-64<5%RA(Refractory Anemia)
Survival (months)
% Blasts in Bone
MarrowCategory
List AF, et al. The Myelodysplastic Syndromes. In: Wintrobe’s Hematology 2003.
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No. PatientsNo. Patients 4343Female predominanceFemale predominance 29 (67)29 (67)Platelets > 150,000/Platelets > 150,000/µµLL 36 (84)36 (84)Dysplastic megakaryocytesDysplastic megakaryocytes 40 (92)40 (92)Erythyroid Erythyroid hypoplasia hypoplasia 38 (90)38 (90)Leukemia evolutionLeukemia evolution 5 (12)5 (12)Median survival*Median survival* >5 years>5 years
Cancer Genet Cytogenetics 1985; 17: 189.Cancer Genet Cytogenetics 1985; 17: 189. *IPSS.*IPSS.
5q- SyndromeHematologic Features
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AML• >20% Blasts•RAEB-t
WHO Classification
MDSMDS•• RARA -- RARA
-- RCMDRCMD•• RARSRARS-- RARS RARS
-- RCMDRCMD--RSRS••RAEBRAEB-- RAEB I (5RAEB I (5--10% Blasts)10% Blasts)
--RAEB II (11RAEB II (11--19% Blasts)19% Blasts)•• OtherOther-- 5q5q-- SyndromeSyndrome
--MDS MDS --UU
MDS/MPDMDS/MPD•• CMML CMML (>13,000/(>13,000/µµL)L)
•• JMMLJMML
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*Good = normal, -Y, del(5q), del(20q); Intermediate = other karyotypic abnormalities; Poor = complex (≥3 abnormalities) or chromosome 7 abnormalities. †Hgb <10 g/dL; ANC <1800/µL; platelets <100,000/µL.RISK: LOW (0), INT-1 (0.5-1.0), INT-2 (1.5-2.0), HIGH (> 2.5)
Greenberg P, et al. Blood. 1997;89:2079-2088.
IPSS Scoring System
• All 3 prognostic variables are required to generate IPSS score
Score Value
2/30/1Cytopenias†
PoorIntermediateGoodKaryotype*
21%-30%11%-20%--5%-10%<5%Bone Marrow Blasts
2.01.51.00.50Prognostic Variable
2323
Survival: MDS vs. Lung CancerSurvival: MDS vs. Lung Cancer
Lung CancerLung CancerMDSMDS
1.21.2IVIV0.40.4HighHigh>2>22.42.4IIIaIIIa1.21.2IntInt--221.51.5--225.45.4IIaIIa3.53.5IntInt--110.50.5--1188IaIa5.75.7LowLow00
Median Median Survival Survival
(Yrs)(Yrs)StageStage
Median Median Survival Survival
(Yrs)(Yrs)
RiskRiskGroupGroup
IPSSIPSSScoreScore
Greenberg P, et al. Blood. 1997:89:2079-2088.Adebonojo et al. Chest 1999: 115:1507-1513
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Supportive CareIncludes:• Transfusions• Antibiotics• Chelation agents• Growth factors
– EPO +/- G-CSF (or GM-CSF)– Treatment with growth factors (EPO + G-CSF) have not
demonstrated improvement in survival and/or reduced risk of transformation to AML in MDS patients
Faderl, S. Myelodysplastic Syndromes. In: Cancer Principles & Practice of Oncology. Philadelphia, PA: Lippincott Williams & Wilkins: 2005: 2144-2154.
EPO=erythropoietin; G-CSF=granulocyte colony-stimulating factor;GM-CSF=granulocyte macrophage colony-stimulating factor.
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Erythropoietin + G-CSF in MDS: Patient Selection
Hellström-Lindberg E, et al. Br J Haematol. 2003;120(6):1037-46.
Good response(74%, n=34)
Intermediate response(23%, n=31)
Poor response(7%, n=29)
s-epo <100 +2U/L 100–500 +1
>500 –3Transf <2 units/m +2U RBC/m = or >2 units/m–2
Treatment response score
RA, RARS, RAEBRA, RARS, RAEB
Score > +1Score > +1
Score –1 to +1Score –1 to +1
Score < –1Score < –1
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RBC Transfusions
• Majority of patients will require transfusion support – Thresholds based on symptoms and comorbidities, not just
hemoglobin level
• Multiple transfusions lead to complications– Allo-sensitization– Iron overload
• Iron chelation for 20-30 units pRBC and prolonged life expectancy
– Oral agent (deferasirox) role unknown in MDS• Increased iron absorption may be seen in RARS
Gordon MS. Semin Hematol. 1999;36(4 Suppl 6):21-4.Tricot GJ, et al. Semin Oncol. 1987;14(4):444-53. http:// www.NCCN.org MDS Guidelines
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Deferasirox Study: Reduction in Ferritin During Study
Timepoint
n=176 n=139 n=113 n=75 n=53
List AF, et al. Blood. 2007;110(11):1470a.
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Deferasirox Study: Unanswered Questions
• Does iron chelation improve survival in MDS?• Would require lengthy, controlled study
• Does iron chelation prevent clinical complications in MDS, as it does in congenital anemias?
• Issues may be distinct for heart vs liver
• In which patient groups is iron chelation cost-effective?
• What is the long-term safety and efficacy profile of deferasirox?
List AF, et al. Blood. 2007;110 (11):1470a.
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MDS Treatment Approaches
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Relapse-free Survival Targeted busulfan and cyclophosphamide
(tBuCy)
Deeg HJ, et al. Blood. 2002;100(4):1201-7.
Relapse-free Survival
0 1 2 3 4 5 6 70
20
40
60
80
100
Years from Transplant
Rel
apse
-free
Sur
viva
l (%
)
IPSS 0 (N=16)/ LIPSS .5-1 (N=54)/ I-1
IPSS 1.5-2 (N=24)/ I-2 IPSS >2 (N=8)/ H
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Approximation of Life Expectancy (Years)
2.752.753.20High
2.843.214.93Int-2
5.164.744.61Int-1
7.216.866.51Low
Transplant at Progression
Transplant in 2 Years
Immediate Transplant
From Cutler C, et al. A Decision Analysis of Allogenetic Bone Marrow Transplantation for Myelodysplastic Syndromes: Delayed Transplantation for Low Risk Myelodysplasia is Associated with Improved Outcome. Blood 2004- 1st Ed Publication. Prepublished online March 23, 2004; D01.1182/Blood-2004-01-0338.Copyright American Society of Hematology, used with Permission.
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The Decision
Time
% S
urvi
val
HCT
No HCT
Cutler C, et al. Blood. 2004;104(2):579-85.
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Available Agents:Indications, Dosing, and MOA
Intravenous infusion (1–3 h)
OralSubcutaneous
Intravenous
Route
45 mg/m2/d x 3 d q 6 wk
10 mg/d75 mg/m2/d x 7 d q 4 wk
Dosing
DNA hypomethylation
All MDS subtypes(FAB classes)
(IPSS: Low, Int-1, Int-2, High)
Azacitidine
DNA hypomethylation
Immune modulation; angiogenesis inhibition
MOA
All MDS subtypes(FAB classes)
IPSS: Int-1, Int-2, HighSecondary MDS
Low-risk MDS(IPSS low or Int-1)with deletion 5q;
Transfusion dependent
Indication
DecitabineLenalidomide
FAB = French-American-British; IPSS = International Prognostic Scoring System.Vidaza [package insert]. Pharmion Corp; 2004.Lyons et al. Poster presented at: ASH 2005 Annual Meeting. Abstract 2517. Revlimid [package insert]. Celgene Corp; 2005.Saba et al. Presentation at: ASCO 2005 Annual Meeting. Abstract 6543.Kantarjian et al. Poster presented at: ASH 2005 Annual Meeting. Abstract 2522.
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Genetics and DNA : “The Code of Life”
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“Genetics and Epigenetics”
The Phillips Sisters: “Ann Landers” and “Dear Abby”
Epigenetics = “Heritable Information not coded for in the DNA Sequence”
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How are genes turned off?…. DNA Methylation
“ON”“OFF” Gene
Protein
DNA
RNA
Protein
Jones PA, et al. Nat Rev Genet. 2002 ;3(6):415-28.
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Epigenetics in Cancer
Normal
DNA Tumor Suppressor Oncogene
Cancer
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How DNA Methyltransferase Inhibitors Work
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• Minimum duration of supportive care=4 months unless transformation to AML; death or platelets <20 x 109/L at week 8 or later
• Growth factors were prohibitedBM=bone marrow.
Supportivecare*
Stratify:• RA• RARS• RAEB• RAEB-T• CMMoL VIDAZA 75 mg/m2/d SC x 7 days every 28 x 4
Exitcriteria
No Continue untilendpoint +
Yes VIDAZA(dose as per arm #2)
ASSESS
Response• Continue Rx
No Response• Off study
BMBM BM0 5729 113
Day
Study 9221: A Randomized Phase III Controlled Trial of Subcutaneous VIDAZA®
(azacitidine for injection) in MDS
Silverman L. The Oncologist. 2001;6:8-14.Silverman LR, et al. J Clin Oncol. 2002;20:2429-2440.Kornblith AB, et al. J Clin Oncol 2002;18:2427-2439.
RANDOMIZE
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Analysis of ResponseSC AZA Crossover
No. Evaluated 92 99 49
CRCR 0 (0%)0 (0%) 77 (7%)(7%)** 5 5 (10%)(10%)
PRPR 0 (0%)0 (0%) 15 15 (16%) (16%) **** 2 2 ( 4%)( 4%)
ImprovedImproved 5 (5%)5 (5%) 38 38 (37%) (37%) **** 16 16 (36%)(36%)
TotalTotal 5 (5%)5 (5%) 6060 (60%) (60%) **** 23 23 (47%)(47%)
P P -- valuevalue * < 0.01* < 0.01 **<0.001**<0.001
Silverman L, et al. Randomized Controlled Trial of Azacitidine in Patients with MDS: A Study of the CALGBJ Clin Oncol 2002. 18:2414-26. Reprinted with permission from the American Society of Clinical Oncology.
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Study 9221: Time to Response
VIDAZA full prescribing information. Data on file, Pharmion Corporation.
• The initial positive effect observed included:*– HgB (18.8%)– Platelets (25%)– WBC (18.8%)– Blasts (37.5%)
* Includes patients with adjudicated baseline diagnosis of AML
*Initial positive effect was defined as the first day of achievement of target for 4 weeks for at least one abnormality.
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Azacitidine Treatment Prolongs Overall Survival in Higher-Risk MDS Patients
Compared with Conventional Care Regimens: Results of the AZA-001 Phase III Study
P P FenauxFenaux, MD, GJ Mufti, MD, V , MD, GJ Mufti, MD, V SantiniSantini, MD, C , MD, C FinelliFinelli, MD, , MD, A A GiagounidisGiagounidis, MD, R , MD, R SchochSchoch, MD,A List, MD, S Gore, MD, , MD,A List, MD, S Gore, MD, J Seymour, MD, E J Seymour, MD, E HellstromHellstrom--Lindberg, MD, J Bennett, MD, Lindberg, MD, J Bennett, MD,
J Byrd, MD, J J Byrd, MD, J BackstromBackstrom, MD, L Zimmerman, BSN, , MD, L Zimmerman, BSN, D McKenzie, MS, CL Beach, D McKenzie, MS, CL Beach, PharmDPharmD and L Silverman, MD and L Silverman, MD
on behalf of the International on behalf of the International VidazaVidaza HighHigh--Risk MDS Risk MDS Survival Study GroupSurvival Study Group
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Azacitidine Survival Study
AZAAZA 75 mg/m75 mg/m22/d x 7 d q28 d/d x 7 d q28 d
CCRCCRRandomizationRandomization
BSC was included with each armTx continued until unacceptable toxicity or AML transformation or disease progression
• Best Supportive Care (BSC) only• Low Dose Ara-C (LDAC,
20 mg/m20 mg/m22/d x 14 d q28/d x 14 d q28--42 d42 d))• Std Chemo (7 + 3)
Screening/CentralPathology Review
Investigator CCRTx Selection
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Overall Survival: Azacitidine vs CCR ITT Population
LogLog--Rank p=0.0001Rank p=0.0001HR = 0.58 [95% CI: 0.43, 0.77]HR = 0.58 [95% CI: 0.43, 0.77]Deaths: AZA = 82, CCR = 113Deaths: AZA = 82, CCR = 113
0 5 10 15 20 25 30 35 40
Time (months) from RandomizationTime (months) from Randomization
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Prop
ortio
n Su
rviv
ing
Prop
ortio
n Su
rviv
ing
CCRCCRAZAAZA
Difference: 9.4 monthsDifference: 9.4 months
24.4 months24.4 months
15 months15 months
50.8%50.8%
26.2%26.2%
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Secondary Endpoints: IWG (2000) RR and HI
1818
1414
11112929
44
881212
CCR CCR N=179N=179
(%)(%)
0.870.872424111120201919HIHI--N MajorN Major
0.00030.00032020191910103333HIHI--P MajorP Major
<0.0001<0.000122221010884040HIHI--E MajorE Major<0.0001<0.00012828252531314949Major+Minor Major+Minor
0.0090.009
0.020.020.00010.0001
PP--ValueValueAZA vs AZA vs
CCRCCR
IWG HIIWG HI
4444441212PRPR
363688111717CRCR40401212552929Overall Overall (CR+PR)(CR+PR)
Std Std Chemo Chemo N=25N=25
(%)(%)
LDAC LDAC N=49N=49
(%)(%)
BSC BSC Only Only
N=105N=105(%)(%)
AZA AZA N=179N=179
(%)(%)ResponseResponse
CCR RegimensCCR Regimens
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Additional Analysis: Median OS by Investigator Selection
0.870.87
0.580.58
0.560.56
Hazard Hazard RatioRatio
0.0020.0029.69.6
21.121.1
11.511.5
AZA (N=117)AZA (N=117)vs vs BSC (N=105)BSC (N=105)
0.750.759.49.4
25.125.1
15.715.7
AZA (N=17) AZA (N=17) vsvsStand Chemo (N=25)Stand Chemo (N=25)
0.0750.0759.29.2
24.524.5
15.315.3
AZA (N=45)AZA (N=45)vs vs LDAC (N=49)LDAC (N=49)
LogLog--rank P rank P
KK--M OS M OS Time Time mosmos
KK--M OS M OS Time Time mosmosTreatmentTreatment
DifferencesDifferences
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Azacitidine extends overall survival (OS) in higher-risk MDS
without the necessity for complete remission
Azacitidine Azacitidine extends overall extends overall survival (OS) in highersurvival (OS) in higher--risk MDS risk MDS
without the necessity for without the necessity for complete remission complete remission
Alan List, Pierre Alan List, Pierre FenauxFenaux, , Ghulam Ghulam Mufti, Eva Mufti, Eva HellstromHellstrom--LindbergLindberg, Steven Gore, John , Steven Gore, John Bennett, Lewis Silverman, Jay Bennett, Lewis Silverman, Jay BackstromBackstrom, and CL Beach on behalf of the , and CL Beach on behalf of the
International International VidazaVidazaHighHigh--Risk MDS Survival Study GroupRisk MDS Survival Study Group
ASCO 2008ASCO 2008
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OS with AZA by Best Response (IWG 2000)OS with AZA by Best Response (IWG 2000)OS with AZA by Best Response (IWG 2000)
0 5 10 15 20 25 30 35 40Time (months) from Randomization
0.0
0.1
0.2
0.3
0.40.5
0.60.7
0.8
0.91.0
Prop
ortio
n Su
rviv
ing
HI
PRCR
SDCCR
DP
24
67.5% (p=0.006)
71.7% (p<0.0001)
41.3% (p=0.041)
78.4% (p<0.0001)
26.2%
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Azacitidine5-azacytidine
Decitabine5-aza-2‘-deoxycytidine
DNARNA
50
Cytidine Analogs
51
Decitabine Phase 3 Study Design
OpenOpen--label, 1:1 randomized, multilabel, 1:1 randomized, multi--center study center study in the US and Canada in the US and Canada
Eligible Patients (n = 170)
Decitabine + Supportive Care* Decitabine + Supportive Care* (n = 89)(n = 89)
RANDOMIZED
Supportive Care*Supportive Care*(n = 81) (n = 81)
Stratification• IPSS Classification• Prior Chemotherapy• Study Center
Study DStudy D--00070007*Antibiotics, Growth Factors and/or TransfusionsSaba HI, et al. J Clin Oncol. 2005;23(suppl 16S):570s. Abstract 6543..
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Decitabine Phase 3 Dose and Administration
Cycle
15 mg/m2
3 hour15 mg/m2
3 hour15 mg/m2
3 hour
135 mg/m2
3 days
6 week cycle
8 hours 8 hours 8 hours
ThreeConsecutive
Days
Schedule: 3 hour infusion q 8 hrs x 3 daysSchedule: 3 hour infusion q 8 hrs x 3 days
Median number of cycles/patient: 3 (Range = 0 Median number of cycles/patient: 3 (Range = 0 -- 9)9)
Study D-0007Saba HI, et al. J Clin Oncol. 2005;23(suppl 16S):570s. Abstract 6543.
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Decitabine Phase III MDS Trial Results
7%13%Hematologic Improvement (IWG)
7%30%Overall Clinical Benefit (CR + PR + Hematologic Improvement)
Not assessed288d (116-388)Median Duration of Response (CR + PR)
Not assessed93d (55-272)Median Time to Response (CR + PR)
0%8%Partial Response0%9%Complete Response0%17%Overall Response (IWG Criteria)†
Supportive Care (N=81)
Decitabine*(N=89)ITT Analysis
†P<0.001.
*FDA approval based on response analysis; decitabine treatment did not significantly delay the median time to AML or death versus supportive care.
Dacogen™ (decitabine for injection) full prescribing information. May, 2006.
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Decitabine Exposure in Phase 2 and 3 Studies
Multiple cycles of decitabine therapy may be required for optimal response
3444Median # cycles
7 (8%)4 (5%)3 (5%)5 (17%) PR
8 (9%)19 (22%)14 (21%)8 (28%) CR
15 (17%)23 (26%)17 (26%)13 (45%)ORR (CR + PR)
89876629N
D-000797-1995-1191-01
Phase 3Phase 2
Saba HI, et al. Saba HI, et al. BloodBlood . 2005;106:706a [abstract 2515]. . 2005;106:706a [abstract 2515]. Kantarjian Kantarjian HM, et al. HM, et al. CancerCancer. 2006;106:1794. 2006;106:1794--1803. Saba HI, et al. 1803. Saba HI, et al. Semin Semin HematolHematol. 2005;42(3 . 2005;42(3 suppl suppl 2): S232): S23--S31. S31. Wijermans Wijermans PW, et al. PW, et al. LeukemiaLeukemia. 1997;11:1. 1997;11:1--5. 5. Wijermans Wijermans PW, et al. PW, et al. J J Clin Clin OncolOncol..2000;18:9562000;18:956--962.962.
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Survival and Efficacy of Decitabine in Myelodysplastic Syndromes (MDS), Analysis of the 5-Day IV Dosing Regimen
ASH 2007 Abstract #115
Hagop Kantarjian, Guillermo Garcia-Manero, Susan O'Brien, Zeev Estrov, Farhad Ravandi, Jorge Cortes, Jianqin Shan, Jan Davisson, Jean-Pierre Issa
clinicaloptions.com/oncology
Clinical Issues and Future Directions in Hematologic Malignancies
Kantarjian H, et al. ASH 2007. Abstract 115.
Patients with intermediate-1, -2, or
high-risk MDS or CMML + leukocytosis;
performance status 0-2
(N = 124)
Decitabine 20 mg/m2 IV over 1 hr daily for 5 days*(n = 93)
Decitabine 20 mg/m2 SQ daily for 5 days*(n = 14)
Decitabine 10 mg/m2 IV over 1 hr daily for 10 days*(n = 17)
*Every 4 weeks up to 24 courses.
Evaluation of 5-Day IV Decitabine Schedule in MDS
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Comparison of outcome and side effects by dose schedule
273120Median days to platelet recovery†
23 (23)14 (14)50 (12)No. courses requiring hospitalization (%)
403535Median days to delivery of subsequent courses
271424Median days to granulocytes recovery*
10.8 (1.9 – 17.7+)9.7 (0.5 – 22.9+)5.4 (1.0 – 20.4+)Median duration of therapy in mos (range)
9
4 (24)
17
10 Day IV
8 5 Median no. courses
3 (21)25 (39)CR / treated (%)
1464n
5 Day SQ5 Day IVParameter
*To 10o 1099/L or above/L or above; †To 50 x 10To 50 x 1099/L or above/L or above; Kantarjian H, et al. Blood. 2006;108(in press). First Edition Paper, prepublished online Aug 1, 2006; DOI 10.1182/blood-2006-05-021162.
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Decitabine Survival vs Intensive Chemotherapy in Higher Risk MDS (Matched Group)
Kantarjian H, et al. Blood, 2007; 110: 42a-43a Abstract 115
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“A Silver Lining from Tragedy…”
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Questions?Allen Yang
USC/Norris Cancer Center
(323) 865-3950
(800) NORRIS1
www.mds-foundation.org
