CAMPUS GROSSHADERN CAMPUS INNENSTADT MEDIZINISCHE KLINIK III STUDIENUPDATE HÄMATOLOGIE AML: STUDIEN DER AMLCG. K. Spiekermann. Frankfurt,

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1 CAMPUS GROSSHADERN CAMPUS INNENSTADT STUDIENUPDATE HÄMATOLOGIE AML: STUDIEN DER AMLCG K. Spiekermann Frankfurt,

2 AMLCG-STUDIES Patients < 60 Years Percent Survival AMLCG 1981 : N = 508 (Censored 84 ) AMLCG 1986 : N = 729 (Censored 267 ) AMLCG 1992 : N = 544 (Censored 282 ) AMLCG 1999 : N = 1204 (Censored 512 ) AMLCG 2004 : N = 175 (Censored 107 ) AMLCG 2008 : N = 164 (Censored 110 ) Years from Start of Therapy IBKF

3 AMLCG-STUDIES Patients 60+ Years Percent Survival AMLCG 1981 : N = 171 (Censored 11 ) AMLCG 1986 : N = 344 (Censored 25 ) AMLCG 1992 : N = 300 (Censored 49 ) AMLCG 1999 : N = 1225 (Censored 233 ) AMLCG 2004 : N = 98 (Censored 41 ) AMLCG 2008 : N = 133 (Censored 74) Years from Start of Therapy IBKF

4 ÜBERBLICK AML: DIAGNOSTIK UND THERAPIE INTENSIV BEHANDELBARE JÜNGERE PATIENTEN Diagnose Prognose ELN Genetik Konsolid. Erhaltung favourable MRD-gesteuerte Postremissionstherapie Konsolid. Erhaltung Int.-1/2 Dosidichte Induktionstherapie unfavorable Allogene SZT Allogene SCT/KMT Induktion Postremissionstherapie

5 DOSE DENSITY conventional Induction d21 d42 Double Induction d21 d42 Dose-Dense Induction

6 Double Induction AML-CG p = 0,04 Büchner AML-CG 81 and 86)

7 DOSE DENSITY conventional Induction d21 d42 Double Induction d21 d42 Dose-Dense Induction

8 AML-CG 2004 Pilot - Overall Survival S-HAM < Days after start of therapy Braess, Blood 2009

9 AML-CG 2008 S-HAM Regimen

10 JUNG ALT AML-CG 2008 Patient Status: S-HAM PL Young [<60 (-70) Years] Allogeneic Stem Cell Transplantation High and intermediate risk of relapse and/or CR i only R off study CR No donor PL TAD HAM Low risk of relapse TAD-9 Consolidation and 3 years of Maintenance Therapy Intervention Phase Follow-up Phase Patient Status: Old [ 60 (-70) Years] S-HAM PL R off study PL CR TAD-9 Consolidation and 3 years of Maintenance Therapy HAM ( HAM) / Intervention Phase KLINIKUM Follow-up DER UNIVERSITÄT Phase MÜNCHEN

11 ORR by therapy: Response Rate No N (%) ORR Yes N (%) N (%) Standard 51 (28) 133 (72) 184 (48) S-HAM 47 (23) 156 (77) 203 (52) 98 (25) 289 (75) 387 (100) ORR Standard = (95%CI for ORR Standard = ) ORR S-HAM = (95%CI for ORR S-HAM = ) ORR (S-HAM - STANDARD) = 5% p = 0,202

12 Results AML-CG 2008 S-HAM + 5% ORR not significant OS / EFS / RFS not significant Dose-dense therapy feasible in general AML population (- 80+)

13 Lessons from AML-CG g vs 3g AraC substantially less toxic no 3g AraC doses in (dose-dense) induction 1g S-HAM with best ED rates in AML-CG studies > 14 days shortening of critical neutropenia

14 AMLCG 2014: CONCEPTS

15 AMLCG 2014: INDUCTION S-HAM R FS-HAI

16 MRD CUTOFF TO PREDICT RELAPSE IN CBF/NPM1 MUTATED AML CBFß-MYH11 RUNX1-RUNX1T1 NPM1 CBFß-MYH11/ ABL ratio RUNX1-RUNX1T1 / ABL ratio NPM1 / ABL ratio Hubmann, Haemaologica 2014 Hubmann (unpublished)

17 MRD DURING THERAPY AND FOLLOW UP

18 AMLCG 2014: POSTREMISSION

19 Acknowledgements LMU AML Working Group München - Prof. Hiddemann - Dr. Metzeler - PD Fiegl - Dr. Hubmann - Prof. Spiekermann - Dr. Lichtenegger - Prof. Subklewe - Dr. Unterhalt - Dr. Baumgartner - Dr. Pastore FLAMSA-Protocol - Klinikum Augsburg - PD Dr. Schmid - University of Essen - Prof. Beelen - University of Munich - Dr Tischer - DKD Wiesbaden - - University of Münster - Prof. Büchner - University of Münster - Prof. Faldum/ Dr.Sauerland - University of Regensburg - Prof. Holler AML Working Group Regensburg - Prof. Braess - Dr. Braess Lab. for Leukemia Diagnostics Prof. Spiekermann Prof. Subklewe PD Fiegl Dr. S. Schneider Dr. Hubmann Clinical Study Center Münster Prof. Faldum/ Dr.Sauerland Dr. Amler, Dr. Görlich ETAL-1-Protocol - University of Dresden - Prof. Bornhäuser - University of Münster - Prof. Stelljes - University of Essen - Prof. Beelen - University of Munich - Dr. Tischer, Prof. Hiddemann AMGEN Herr Martin