Neue Perspektiven in der Therapie Follikulrer Lymphome

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Neue Perspektiven in der Therapie Follikulärer
Lymphome
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Rituximab Chemotherapy Combinations
OR
PFS
OS
CVP 57 15 mo 85
R-CVP 81 (plt0.001) 32 mo (plt0.001) 89
(p0.22) Marcus et al. 2005 CHOP
90 31 mo 90
R-CHOP 96 (p0.011) n.r.
(p0.0006) 95 (p0.016) Hiddemann et al.
2005 MCP 75
26 mo 74 R-MCP 92
(p0.0009) n.r. (plt0.0001) 87
(p0.0096) Herold et al. 2007 CHVPIFN
72 35 mo 79 R-CHVPIFN 81
(plt0.0001) n.r. (plt0.0001) 84
(p0.029) Salles et al. 2008
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CHOP versus R-CHOP for First-Line Therapy Time to
Treatment Failure
1.0 0.8 0.6 0.4 0.2 0
R-CHOP (120/135)
Randomised R-CHOP (216/283)
Randomised CHOP (145/276)
plt0.0001
0 1 2 3 4 5 6
Years after start of therapy
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CHOP versus R-CHOP for First-Line Therapy Overall
Survival
RandomisedR-CHOP (270/283)
R-CHOP (131/135)
1.0 0.8 0.6 0.4 0.2 0
Randomised CHOP (248/276)
p0.0101
0 1 2 3 4 5 6
Years after start of therapy
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Key Steps in Improving Treatment for Follicular
Lymphoma
Cure
Prolongation of Life
Palliation of Symptomes
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Comparison of Two Consecutive Study Generations
of the GLSG
R a n d o m i z a t i o n
CHOP
R a n d o m i z a t i o n
pts. lt 60 yrs
MCP
PBSCT
GLSG 1996
IFN-maintenance
GLSG 2000
R a n d o m i z a t i o n
6 - 8 x CHOP Ritux
pts. gt 60 yrs
IFN-maintenance
6 - 8 x CHOP
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Comparison of Two Consecutive Study Generations
of the GLSG
Time to Treatment Failure
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Comparison of Two Consecutive Study Generations
of the GLSG
Overall Survival
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Future Strategies in Follicular Lymphomas
Therapy in Remission
Induction
Maintenance
ASCT
No further Therapy
Chemotherapy plus Rituximab
gt Lymphoma Reduction
gt Lymphoma Control
email_at_med.uni-muenchen.de
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FLIPI and Time to Treatment Failure
low
intermediate
high
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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

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PRIMA Study 2005 Follicular Lymphomas
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OSHO/GLSG Study 2007 Follicular Lymphomas Not
eligible for PBCT or Age gt 65 Yrs.
R
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FIT 90Y-ibritumomab tiuxetan as first-line
consolidation
90Y-ibritumomab tiuxetan (n208)
Induction chemotherapy
Newly diagnosed follicular lymphoma stage
III/IV
CRPR

R
watch wait (n206)
NR PD
off study
R
Randomisierung
FIT First-line Indolent lymphoma Trial CVP,
CHOP, Fludarabin (combination), etc. n 414
Hagenbeek, ASH 2007110 abstr 643
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FIT 90Y-ibritumomab tiuxetan as first-line
consolidation
Progression-free survival
Log rankp lt 0.0001HR 0.463
90Y-ibritumomab tiuxetanmedian 37 mo (n208)
Control median 13.5 mo(n206)
Hagenbeek, ASH 2007110 abstr 643
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GLSG Study 96
pts. lt 60 yrs. (lt65yrs.)
R a n d o m i z a t i o n
R a n d o m i z a t i o n
PBSCT
6 - 8 x MCP
CR,PR
standard IFN-maintenance
pts. gt 60 yrs. (gt65 yrs.)
6 - 8 x CHOP
intensive IFN-maintenance
CR,PR
standard IFN-maintenance
Hiddemann et al., Blood 2005
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GLSG Progression free Survival
Lenz et al., Blood 2004
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ASCT in 1st Remission Analysis from two
Consecutive Study Generations of the GLSG
R a n d o m i z a t i o n
6 8 x CHOP
R a n d o m i z a t i o n
pts. lt 60 yrs
6 8 x MCP
ASCT
GLSG 1996
IFN-maintenance
GLSG 2000
R a n d o m i z a t i o n
6 - 8 x CHOP Ritux
pts. gt 60 yrs
IFN-maintenance
6 - 8 x CHOP
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ASCT in 1st Remission Analysis from two
Consecutive Study Generations of the GLSG
R a n d o m i z a t i o n
6 8 x CHOP
R a n d o m i z a t i o n
pts. lt 60 yrs
6 8 x MCP
ASCT
GLSG 1996
IFN-maintenance
GLSG 2000
R a n d o m i z a t i o n
6 - 8 x CHOP Ritux
pts. gt 60 yrs
IFN-maintenance
6 - 8 x CHOP
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GLSG Studies 1996 and 2000Response Duration
12-03
1.0 0.8 0.6 0.4 0.2 0
CHOP PBSCT 00
R-CHOP PBSCT 00
CHOP PBSCT 96
R-CHOP IFN 00
CHOP IFN 00
Probability
CHOP IFN 96
0 1 2 3 4 5 6 7
Years after end of induction therapy
December 2003
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GLSG Studies 1996 and 2000Response Duration 12-06
1.0 0.8 0.6 0.4 0.2 0
R-CHOP PBSCT (81/94)
R-CHOP IFN (105/126)
CHOP PBSCT (95/137)
Probability
CHOP IFN (48/160)
0 1 2 3 4 5 6 7 8 9 10
Years after end of induction therapy
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GLSG Studies 1996 and 2000Response Duration 08-08
R/ASCT ASCT R/IFN IFN
1.0 0.8 0.6 0.4 0.2 0
Probability
plt0.0001
0 12 24 36 48 60 72 84 96 108 120
Month after end of induction
No. of patients at riskR/ASCT 116 97 76
52 39 26 7 0 ASCT 145 132 118 107 87 69 54 38
22 12 R/IFN 152 120 86 62 32 17 5
0 IFN 167 114 85 62 44 36 28 17 9 2
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CHOP vs. R-CHOP /-PBSCT 1524 patients randomized
156 not randomized 13 MRD data

861 first randomization
433 randomized R-CHOP
553 assigned to R-CHOP
428 randomized to CHOP

418 treated R-CHOP
436 treated R-CHOP
411 treated CHOP








224 MRD data 172 R-CHOP 52 no treatment documented
100 MRD data 98 CHOP 2 no treatment documented
145 MRD data 142 R-CHOP 3 treated with CHOP
490 MRD data 327 R-CHOP 108 CHOP 54 no
treatment documented
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Quantitative t(1418) AnalysisMRD levels at
induction
CHOP Induction p0,0021
R-CHOP Induction plt0,0001
15
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72
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Remission Duration according to
Consolidation(n30, MRD negative after
induction)
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Remission Duration according to Consolidation
MRD neg.
MRD pos.
UK SH
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RiCHOP study 2009 for First-Line Therapy of FL
Patients aged lt65 Years
R A N D O M I S A T I O N
ASCT
CR,PR
6 x CHOP 8 x R
Rituximab maintenance
Rituximab maintenance
CR,PR
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RiCHOP study 2009 for First-Line Therapy of FL
Patients aged lt65 Years

• Ultimate Goal Cure
• by combining all proven effective treatment
  modalities
• R-chemo for initial therapy
• ASCT
• R maintenance
• The Concept of Total Therapy

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Key Steps in Improving Treatment for Follicular
Lymphoma
Cure
Prolongation of Life
Palliation of Symptomes
email_at_med.uni-muenchen.de
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GLSG Study Group
Supported by Deutsche Krebshilfe