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email@med.uni-muenchen.de
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
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
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
email@med.uni-muenchen.de
Palliationof Symptomes
Prolongation of Life
Cure
Key Steps in Improving Treatment for Follicular Lymphoma
email@med.uni-muenchen.de
Future Strategies in Follicular Lymphomas
Induction
Therapy in Remission
Maintenance
ASCT
=> Lymphoma Control=> Lymphoma Reduction
Chemotherapy plus RituximabNo further Therapy
FLIPI and Time to Treatment Failure
low
intermediate high
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
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
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.
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
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
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
Lenz et al., Blood 2004
GLSG – Progression free Survival
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
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
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
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
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
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
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%
Remission Duration according to Consolidation(n=30, MRD negative after induction)
UKSH
Remission Duration according to Consolidation
MRD neg. MRD pos.
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
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
email@med.uni-muenchen.de
Palliationof Symptomes
Prolongation of Life
Cure
Key Steps in Improving Treatment for Follicular Lymphoma
Supported byDeutsche Krebshilfe
GLSG Study Group