influence of mutational status in cll after autologous ... · cart19 phase-1/2 amg all, cll, nhl...

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Allogene Stammzelltransplanta0on: JAHRESBERICHT 2017 Sek0on Stammzelltransplanta0on | Klinik Innere Medizin V | Universitätsklinikum Heidelberg | Prof. Dr. Peter Dreger

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Page 1: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Allogene  Stammzelltransplanta0on:  

JAHRESBERICHT  2017   Sek0on  Stammzelltransplanta0on  |  Klinik  Innere  Medizin  V  |  Universitätsklinikum  Heidelberg  |   Prof.  Dr.  Peter  Dreger  

     

Page 2: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Patienten

Page 3: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

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Erwachsene Kinder

Allogene Transplantationen

118

6

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

Page 4: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

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Unverwandt Verwandt Haplo

Spender

Page 5: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

0

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AML/MDS

ALL

Lymph./CLL

Myelom/Amyl

MPS/CML

Sonst. Npl.

Sonstige

Indikationen

Page 6: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

Zuweiser 2017

Ext. Zuweiser I.O. Sonstige

Page 7: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

2017:

5 Pat. >70J,

max. 73J

NRM = 20%

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70

2005

2006

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2008

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Medianes Patientenalter

Page 8: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

0 6 12 18 24

0

20

40

60

80

1002005-2007 (202)

2016-2017 (212)

100d: 5%1-y: 13%

100d: 4%1-y: 13%

Months

% N

RM

Non-relapse mortality by period

Page 9: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

Overall survival by period

0 180 360 540 720

0

20

40

60

80

100

2005-2007 (202)

2016-2017 (212)

Days

% S

urv

ival

Page 10: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Forschung und ihre Implikationen

Page 11: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

AlloHCT: Trial activity

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

Study Study type Topic PI HD Sponsor n

MC Flud T14 Phase-3 AMG BuFlu vs TreoFlu Luft medac 52

Letermovir Phase-3 AMG CMV-Prophylaxe Schmitt MSD 19

LFG Phase-2/3 AMG TMA Luft Novartis 3

STUD RIG Phase-2 AMG Ref aGVHD Dreger UK FR 2

TFT2 Phase-2 AMG Zweit-allo AML Dreger UK FR 7

CHARLY Phase-2 AMG NHL haplo Dietrich UK HD 2

CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD -

DP matching Observational DP matching P Dreger UK Essen 40

Restmaterial Biobank GVHD, TMA etc Luft selbst 700+

Page 12: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

MK8228 Ph-III RCT

(Marty et al, ASBMT2017)

Page 13: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

• EU-Verfügbarkeit ab 15.02.2018

Page 14: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

AlloHCT: Trial activity

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

Study Study type Topic PI HD Sponsor n

MC Flud T14 Phase-3 AMG BuFlu vs TreoFlu Luft medac 52

Letermovir Phase-3 AMG CMV-Prophylaxe Schmitt MSD 19

LFG Phase-2/3 AMG TMA Luft Novartis 3

STUD RIG Phase-2 AMG Ref aGVHD Dreger UK FR 2

TFT2 Phase-2 AMG Zweit-allo AML Dreger UK FR 8

CHARLY Phase-2 AMG NHL haplo Dietrich UK HD 2

CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD -

DP matching Observational DP matching P Dreger UK Essen 40

Restmaterial Biobank GVHD, TMA etc Luft selbst 700+

Page 15: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

HR-AML: Aplasie- vs TFT-Konditionierung (2014-2017)

0 6 12 18 24 30 36

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100Aplasia (61)

TFT (11)

Months from HCT

% S

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ival

0 6 12 18 24 30 36

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100Aplasia (61)

TFT (11)

Months from HCT

% R

FS

0 6 12 18 24 30 36

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100Aplasia (61)

TFT (11)

Months from HCT

% N

RM

• Aplasie: alle refraktär oder unbehandelter REL

• TFT: alle Zweit-allo; 9/11 refraktär

Page 16: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

Aplasia conditioning in R/R AML: Impact of conditioning regimens

0 6 12 18 24 30 36

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100HR araC-based (31)

CLARA-based (30)

Months from HCT

% R

FS

0 6 12 18 24 30 36

0

20

40

60

80

100other (54)

CLARA/TBI >4 (7)

Months from HCT

% R

FS

Page 17: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

AlloHCT: Trial activity

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

Study Study type Topic PI HD Sponsor n

MC Flud T14 Phase-3 AMG BuFlu vs TreoFlu Luft medac 52

Letermovir Phase-3 AMG CMV-Prophylaxe Schmitt MSD 19

LFG Phase-2/3 AMG TMA Luft Novartis 3

STUD RIG Phase-2 AMG Ref aGVHD Dreger UK FR 2

TFT2 Phase-2 AMG Zweit-allo AML Dreger UK FR 8

CHARLY Phase-2 AMG NHL haplo Dietrich UK HD 2

CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD -

DP matching Observational DP matching P Dreger UK Essen 51

Restmaterial Biobank GVHD, TMA etc Luft selbst 700+

Page 18: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial
Page 19: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

EASIX: LDH (U/l) x creatinine (mg/dl)

Platelets/nl

Page 20: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial
Page 21: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial
Page 22: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial
Page 23: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial
Page 24: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Impact

Page 25: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

Jahr Artikel Erstautor Journal Zitate

2007 EBMT CLL transplant consensus Dreger Leukemia 433

2010 GCLLSG CLL3X trial outcome Dreger Blood 269

2008 Allo-SCT in 17p- CLL EBMT Schetelig JCO 177

2014 Managing high-risk CLL in transition Dreger Blood 126

2011 Refractory GVHD and endothelial markers Luft Blood 94

2007 CK18F as GVHD markers Luft Blood 73

Heidelberg alloHCT program: Top cited publications

• Impact 2017 (Erst- u/o Letztautor a.d. Sektion): 104,215

• Impact 2017 (Koautor aus der Sektion): 109,893

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Veranstaltungen

Page 27: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial
Page 28: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Es tut sich was…

Page 29: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

…mit den CARTS

Page 30: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial
Page 31: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

ZUMA-1 trial

Page 32: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

Investigator Initiated Trial (IIT)

Pharma-derived CARs

In-label Clinical trials

NCT-HD-CAR-1 Novartis

Miltenyi

GMP vector production by Prof. Brenner, BCM

GMP leukapheresis by UKHD – Med. V GMP culture & transduction by GMP lab Med V (M Schmitt) GCP application on HIS

Kymriah™ CD19+ ALL < 26 y/o

ZUMA-7 CD19+ DLBCL

Melanoma CD20

Kite/ Gilead

Kite/ Gilead

Yescarta™ CD19+ DLBCL ≥ 18 y/o

Celgene

BCMA+ Multiple Myeloma

Novartis

BCMA+ Multiple Myeloma

…mit den CARTs in Heidelberg

Page 33: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

…mit den CARTs in Heidelberg

• NCT-HD-CAR1: CD19 all comer, IIT, Sponsor UKHD, LKP M Schmitt – Start Q2/3 2018

• ZUMA-7: DLBCL 1. Relapse, Sponsor Kite/Gilead, LKP P Dreger – Start Q3 2018

• Yescarta: DLBCL, zugelassene Indikation, Launch in HD Q3/2018 (als 1. Zentrum in DE)

Page 34: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial

“Allo” sind… „von Dusch“ M Lommatzsch A Dugimont ...und das Team!

Koordination P Stadtherr I Opitz A Herrmann

Ambulanz T Luft S Schönland A Radujkovic J Brandt M Cremer S Gröschel S Raffel J Tate S Zink

Case Manager A Bondong M Wegner

Labor T Luft S Dietrich M Hess A Radujkovic A Hof R Schulz S Kräker

Sozialdienst A Bergner G Daiß S Sontowski

Anleitung U Hegenbart P Dreger

…und natürlich auch K Jordan C Müller-Tidow

...alle Mitarbeiter der MedV !

Sucheinheit H Tran K Nerbel & Team

Psychologie D Tönnessen

Station M Schiller S Kierschke D Finke N Liebers C Pabst K Pashayeva N Payer ML Schubert H Veelken A Hoffmann A Martin

Studienzentrale J Klemmer AM Geueke & Team

Sport R Kühl J Wiskemann & Team

ECP A Schmitt R Alexi & Team

CART M Schmitt A Schmitt & Team

Universitätsklinikum Heidelberg | 19.02.2018 | Prof. Dr. Peter Dreger

I.O. und andere Affairs M Geiss JW Schmier

Page 35: Influence of mutational status in CLL after autologous ... · CART19 Phase-1/2 AMG ALL, CLL, NHL Schmitt UK HD - DP matching Observational DP matching P Dreger UK Essen 51 Restmaterial