ASCO O 2009 Leukemias, MDS S, Transplantation EJ Feldm man M.D. - PowerPoint PPT Presentation

ASCO O 2009 Leukemias, MDS S, Transplantation EJ Feldm man M.D. Weill-Cornell M Weill Cornell M Medical College Medical College

AML: Karyotype AML: Karyotype e and Prognosis e and Prognosis Results From ECOG 348 Results From ECOG 348 89/SWOG 9034 89/SWOG 9034 Overall Survival Patients Age 16 Overall Survival Patients Age 16 6-55 With Untreated AML 55 With Untreated AML 100% 100% 100% 100% At Risk At Risk Deaths Deaths Estimate (CI) at 5 years Estimate (CI) at 5 years (C ) (C ) Favorable Favorable 12 12 53 53 55% (45 55% (45- -64%) 64%) N = 609 N = 609 Intermediate Intermediate 278 278 168 168 38% (32 38% (32- -44%) 44%) 80% 80% Unfavorable Unfavorable 184 184 162 162 1 11% (7 1% (7- -16%) 16%) 60% 60% 40% 40% Heterogeneity Heterogeneity y of 3 groups: P < 0.0001 y of 3 groups: P < 0.0001 20% 20% 0% 0% 0 2 2 4 6 6 8 8 Years After Ente Years After Ente ering Study ering Study 2 Slovak ML, et al. Slovak ML, et al. Blood. Blood. 2000;96:4075 2000;96:4075- -4083. 4083.

Abstract Abstract t # 7000 t # 7000 NPM1 Mutatio ns in CN AML • CN AML: Largest # of Pts • Intermediate Prognosis-- Intermediate Prognosis --25-40% cure rate 25 40% cure rate • Flt-3 and NPM1 prognos stic in Pts < age 60 • ? Prognostic value in ol lder Patients

CN AML in CR1: out CN AML in CR1: out tcome by mutational tcome by mutational anal anal l ysis ysis i Schlenk et al NEJM 2008 Schlenk et al NEJM 2008

NPM1 Mutations in AML > age 60 • 189 AML Pts > age 60 • Rx with dauno/ara-c regime g en • Multivariate analysis—i ndependent variable NPM1 mut NPM1wt P value CR% 84 48 <0.001 3 yr DFS% 23 10 0.047 3 yr OS% 35 8 <0.001

Abstrac Abstrac ct 7015 ct 7015 FLT3 Mutations in CG G subgroups of AML • 481 AML patients—retr rospective review • Most common in CN gro Most common in CN gro oup (32%) oup (32%) • Uncommon in poor risk CG (7.6%) • OS unaffected in good a and poor risk CG groups • Confirmed prognostic ef effect in CN group

Abstract 7002: Abstract 7002: Molecular Risk Molecular Risk Classification in n AML < age 60 • NPM1 Flt-3 mutational s status prognostic in CN AML • Other mutations: CEBPA WT1 CEBPA, WT1 • Over expression: BAALC, ERG *** Prognostic classificati g on improved p

Abstract 7003 Is ther Abstract 7003 Is ther re a benefit to higher re a benefit to higher yclines in AML ? doses of anthracy • ECOG E1900 • Daunorubicin 90 mg/m2 Daunorubicin 90 mg/m2 2 vs 45 mg/m2 in 2 vs 45 mg/m2 in traditional 3+7 regimen • Denovo AML ages 16 6 • Denovo AML ages 16-6 60 yrs ( median 48 yrs) 60 yrs ( median 48 yrs) • Post-remission Rx varied d ( Hidac, Allo/auto SCT)

Survival EC COG E1900 Dauno 45mg/m2 Dauno 90 mg/m2 P value Median OS (months) 15.7 23.7 0.003 < age 55 (n=459) g ( ) 16.5 28.6 0.002 > Age 55 (n=174) 12.6 16.3 0.63 Median OS (months) Fav/int CG (n=358) 20.7 34.3 0.004 Unfav CG (n=122) 10.2 10.4 0.45 Median OS ( months) Median OS ( months) FLT3mut (n=147) 10.2 15.2 0.3 FLT3wt (n=256) 18.9 28.6 0.002

Abstr Abstr act 7007 act 7007 Dasatinib for imatinib- -resistant/intolerant CML • Dasatinib 100 mg daily— —optimal dose/schedule • Actuarial 36 month foll Actuarial 36 month foll ow-up: ow up: CCR 50% MMR 39% MMR 39% PFS 81% (77%-Pts w with bcr/abl mut) OS 91%

Abstrac Abstrac ct 7010 ct 7010 Decitabine in elderly AML • Phase 2 single institution n trial • 33 patients median age 33 patients, median age 74 74 • CR in 14/33 42% • Median follow-up 8 mon M di f ll 8 nths h

AML > ag AML > ag AML > ag AML > ag ge 60 yrs ge 60 yrs ge 60 yrs ge 60 yrs Regimen # Patients Median age CR % Median surv. Low-dose ara-c 116 74 yrs 18% 6 months Decitabine 5d 55 70 yrs 24% 7 months Azacytidine Azacytidine 20 20 68 yrs 68 yrs 20% 20% NA NA Decitabine 10d 33 74 yrs 42% NA Clofarabine 116 71 Yrs 38% NA Cloretazine 140 74 yrs 29% 3 months Dauno/ara-c 120 70 yrs 43% 7 months

Abstrac Abstrac ct 7011 ct 7011 Decitabine in a advanced MDS Study Med# CR% OR% Tim me to PFS OS TI Red cycles AM ML/death (months) (months) % 3-days 3 9 30 10 7.3 12.8 23 D-0007 (n=89) EORTC 4 13 34 8.8 6.6 10.1 32 (n=119) 5-days 5 15 43 12. 1 8.1 17.8 33 Daco-020 Daco 020 (n=99) IDD3 IDD3 7 7 37 37 65 65 15 2 15.2 2 2 9 2 9.2 20 3 20.3 NA NA (n=93)

Abstracts 7 Abstracts 7 7043/7044 7043/7044 Ofatumum mab in CLL • New anti-CD20 monoclo onal antibody • More active in CDC of B More active in CDC of B B cells than rituximab B-cells than rituximab • 138 refractory CLL patie ents: Double refractory (flu D bl f (fl ud+alemtuzumab) d l b) Bulky flud refractory • 2 gms weekly X 8 and th hen monthly X 4 doses

Ofatumum mab in CLL • ORR 58% • Improvement in Sx’s ad Improvement in Sx s, ad denopathy denopathy, organomegaly, blood co unts. • Median OS 13 7 months • Median OS 13.7 months s • No influence by prior ri ituximab Rx