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[email protected] Neue Perspektiven in der Therapie Follikulärer Lymphome

Neue Perspektiven in der Therapie Follikulärer Lymphome

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Neue Perspektiven in der Therapie Follikulärer Lymphome. Rituximab – Chemotherapy Combinations. OR. PFS. OS. CVP 57 %15 mo 85 % R-CVP81 % (p

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Page 1: Neue Perspektiven in der Therapie Follikulärer Lymphome

[email protected]

Neue Perspektiven in der Therapie Follikulärer Lymphome

mkrych
Name oben links: Diesen Namen müssen wir flexibel verändern können! Bitte als zugänglichen Text formatieren. Außerdem ist der RICHTIGE Namen um Augenblick: Medizinische Klinik und Poliklinik III - GroßhadernKlinikum der Universität MünchenLogos oben rechts: Diese Logos müssen wir flexibel verändern können! Bitte als verschiebbare / veränderbare Symbole in den Master integrieren.
Page 2: Neue Perspektiven in der Therapie Follikulärer Lymphome

CVP 57 % 15 mo 85 % R-CVP 81 % (p<0.001) 32 mo (p<0.001) 89 % (p=0.22)

Marcus et al. 2005

CHOP 90 % 31 mo 90 %R-CHOP 96 % (p=0.011) n.r. (p=0.0006) 95 % (p=0.016)

Hiddemann et al. 2005

MCP 75 % 26 mo 74 %R-MCP 92 % (p=0.0009) n.r. (p<0.0001) 87 % (p=0.0096)

Herold et al. 2007

CHVP+IFN 72 % 35 mo 79 %R-CHVP+IFN 81 % (p<0.0001) n.r. (p<0.0001) 84 % (p=0.029)

Salles et al. 2008

OR PFS OSRituximab – Chemotherapy Combinations

Page 3: Neue Perspektiven in der Therapie Follikulärer Lymphome

CHOP versus R-CHOP for First-Line Therapy Time to Treatment Failure

Randomised R-CHOP (216/283)

Randomised CHOP

(145/276)

Years after start of therapy

R-CHOP (120/135)

1.0

0.8

0.6

0.4

0.2

0 0 1 2 3 4 5 6

p<0.0001

Page 4: Neue Perspektiven in der Therapie Follikulärer Lymphome

RandomisedR-CHOP (270/283)

Randomised CHOP (248/276)p=0.0101

R-CHOP (131/135)

Years after start of therapy

1.0

0.8

0.6

0.4

0.2

0 0 1 2 3 4 5 6

CHOP versus R-CHOP for First-Line Therapy Overall Survival

Page 5: Neue Perspektiven in der Therapie Follikulärer Lymphome

[email protected]

Palliationof Symptomes

Prolongation of Life

Cure

Key Steps in Improving Treatment for Follicular Lymphoma

Page 6: Neue Perspektiven in der Therapie Follikulärer Lymphome

[email protected]

Future Strategies in Follicular Lymphomas

Induction

Therapy in Remission

Maintenance

ASCT

=> Lymphoma Control=> Lymphoma Reduction

Chemotherapy plus RituximabNo further Therapy

Page 7: Neue Perspektiven in der Therapie Follikulärer Lymphome

FLIPI and Time to Treatment Failure

low

intermediate high

Page 8: Neue Perspektiven in der Therapie Follikulärer Lymphome

Follicular Lymphomas Questions for the Next Steps of Therapy

• Value of R maintenance after R chemo in first line therapy

• Best chemotherapy to be combined with Rituximab

• Value of radio-immuno therapy• Value of stem cell transplantation after R

chemo

Page 9: Neue Perspektiven in der Therapie Follikulärer Lymphome

PDs/SDsoff study

follicular NHLstages III–IV,

untreated

Maintenance (SAKK)1 dose q 2 months for

24 months

Observation

R CR/PR6 x CHOP6 x FCM6 x COPplus 8 x R

PRIMA Study 2005 Follicular Lymphomas

Page 10: Neue Perspektiven in der Therapie Follikulärer Lymphome

PDs/SDsoff study

follicular NHLstages III–IV,untreated

Maintenance (SAKK)1 dose q 2 months for

24 months

Observation

R CR/PR

6 x CHOP6 x FCM6 x MCPplus 8 x R

R

OSHO/GLSG Study 2007Follicular Lymphomas

Not eligible for PBCT or Age > 65 Yrs.

Page 11: Neue Perspektiven in der Therapie Follikulärer Lymphome

90Y-ibritumomab tiuxetan(n=208)Induction

chemotherapy*

Newly diagnosed follicular

lymphoma stage III/IV

CRPR

NRPD off study

watch & wait(n=206)

** R

FIT: 90Y-ibritumomab tiuxetan as first-line consolidation

FIT: First-line Indolent lymphoma Trial* CVP, CHOP, Fludarabin (combination), etc.** n = 414

R Randomisierung

Hagenbeek, ASH 2007;110: abstr 643

Page 12: Neue Perspektiven in der Therapie Follikulärer Lymphome

0

20

40

60

80

100

0 6 12 18 24 30 36 42 48 54 60 66

PFS time from randomization (months)

Prop

ortio

n re

mai

ning

pr

ogre

ssio

n fr

ee (%

)

Log rankp < 0.0001HR 0.463

90Y-ibritumomab tiuxetan:median 37 mo (n=208)

Control: median 13.5 mo(n=206)

Progression-free survival

FIT: 90Y-ibritumomab tiuxetan as first-line consolidation

Hagenbeek, ASH 2007;110: abstr 643

Page 13: Neue Perspektiven in der Therapie Follikulärer Lymphome

Randomization

6 - 8 x CHOP

6 - 8 x MCP

CR,PR

CR,PR

Randomization

PBSCT

standard IFN-maintenance

intensive IFN-maintenance

standard IFN-maintenance

pts. < 60 yrs. (<65yrs.)

pts. > 60 yrs. (>65 yrs.)

Hiddemann et al., Blood 2005

GLSG Study `96

Page 14: Neue Perspektiven in der Therapie Follikulärer Lymphome

Lenz et al., Blood 2004

GLSG – Progression free Survival

Page 15: Neue Perspektiven in der Therapie Follikulärer Lymphome

ASCT in 1st Remission: Analysis from two Consecutive Study Generations of the GLSG

Randomization

Randomization

6 - 8 x CHOP +

Ritux

6 - 8 x CHOP

6 – 8 x CHOP

6 – 8 x MCP

Randomization

ASCT

IFN-maintenance

IFN-maintenance

pts. < 60 yrs

pts. > 60 yrs

GLSG 1996GLSG 2000

Page 16: Neue Perspektiven in der Therapie Follikulärer Lymphome

ASCT in 1st Remission: Analysis from two Consecutive Study Generations of the GLSG

Randomization

Randomization

6 - 8 x CHOP +

Ritux

6 - 8 x CHOP

6 – 8 x CHOP

6 – 8 x MCP

Randomization

ASCT

IFN-maintenance

IFN-maintenance

pts. < 60 yrs

pts. > 60 yrs

GLSG 1996GLSG 2000

Page 17: Neue Perspektiven in der Therapie Follikulärer Lymphome

GLSG Studies 1996 and 2000Response Duration 12-03

Years after end of induction therapy

1.0

0.8

0.6

0.4

0.2

0 0 1 2 3 4 5 6 7

CHOP + IFN ’00

CHOP + IFN ’96

CHOP + PBSCT ’96

CHOP + PBSCT ’00

R-CHOP + PBSCT ’00

R-CHOP + IFN ’00

December 2003

Prob

abili

ty

Page 18: Neue Perspektiven in der Therapie Follikulärer Lymphome

Years after end of induction therapy

1.0

0.8

0.6

0.4

0.2

0 0 1 2 3 4 5 6 7 8 910

R-CHOP + PBSCT (81/94)

CHOP + IFN (48/160)

R-CHOP + IFN (105/126)

CHOP + PBSCT (95/137)

Prob

abili

tyGLSG Studies 1996 and 2000

Response Duration 12-06

Page 19: Neue Perspektiven in der Therapie Follikulärer Lymphome

1.0

0.8

0.6

0.4

0.2

0

Prob

abili

ty

No. of patients at riskR/ASCT 116 97 76 52 39 26 7 0ASCT 145 132 118 107 87 69 54 38 22 12R/IFN 152 120 86 62 32 17 5 0IFN 167 114 85 62 44 36 28 17 9 2

Month after end of induction0 12 24 36 48 60 72 84 96 108 120

R/ASCTASCTR/IFNIFN

p<0.0001

GLSG Studies 1996 and 2000Response Duration 08-08

Page 20: Neue Perspektiven in der Therapie Follikulärer Lymphome

100 MRD data98 CHOP

2 no treatment documented

553 assigned to R-CHOP

418 treated

R-CHOP

436 treated R-CHOP

145 MRD data142 R-CHOP

3 treated with CHOP

224 MRD data172 R-CHOP

52 no treatment documented

490 MRD data327 R-CHOP 108 CHOP54 no treatment documented

433 randomized R-CHOP

428 randomized to CHOP

861 first randomization

411 treatedCHOP

156 not randomized13 MRD data

CHOP vs. R-CHOP +/-PBSCT1524 patients randomized

Page 21: Neue Perspektiven in der Therapie Follikulärer Lymphome

Quantitative t(14;18) AnalysisMRD levels at induction

10 -5

10 -4

10 -3

10 -2

10 -1

10 0

MR

D le

vel

neg

R-CHOP Induction p<0,0001CHOP Induction p=0,0021

Diagnosis

p=0,0134

Induction 2

28%

Induction 4 Induction 6

74%28% 72% 15%

Page 22: Neue Perspektiven in der Therapie Follikulärer Lymphome

Remission Duration according to Consolidation(n=30, MRD negative after induction)

Page 23: Neue Perspektiven in der Therapie Follikulärer Lymphome

UKSH

Remission Duration according to Consolidation

MRD neg. MRD pos.

Page 24: Neue Perspektiven in der Therapie Follikulärer Lymphome

6 x CHOP+ 8 x R

CR,PR

CR,PR

RANDOMISATION

ASCT

Rituximab maintenance

Rituximab maintenance

RiCHOP study 2009 for First-Line Therapy of FL Patients aged <65 Years

Page 25: Neue Perspektiven in der Therapie Follikulärer Lymphome

Ultimate Goal : Cure

by combining all proven effective treatment modalities

• R-chemo for initial therapy • ASCT• R maintenance

The Concept of „Total Therapy“

RiCHOP study 2009 for First-Line Therapy of FL Patients aged <65 Years

Page 26: Neue Perspektiven in der Therapie Follikulärer Lymphome

[email protected]

Palliationof Symptomes

Prolongation of Life

Cure

Key Steps in Improving Treatment for Follicular Lymphoma

Page 27: Neue Perspektiven in der Therapie Follikulärer Lymphome

Supported byDeutsche Krebshilfe

GLSG Study Group