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Neue Perspektiven in der Therapie Follikulärer Lymphome

Neue Perspektiven in der Therapie Follikulärer Lymphome. Rituximab – Chemotherapy Combinations. OR. PFS. OS. CVP 57 % 15 mo 85 % R-CVP 81 % (p<0.001) 32 mo (p<0.001) 89 % (p=0.22) Marcus et al. 2005

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Neue Perspektiven in der Therapie Follikulärer Lymphome

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  1. email@med.uni-muenchen.de Neue Perspektiven in der Therapie Follikulärer Lymphome

  2. Rituximab – Chemotherapy Combinations OR PFS OS CVP 57 % 15 mo 85 % R-CVP 81 % (p<0.001) 32 mo (p<0.001) 89 % (p=0.22) Marcus et al. 2005 CHOP90 % 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

  3. 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) p<0.0001 0 1 2 3 4 5 6 Years after start of therapy

  4. 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) p=0.0101 0 1 2 3 4 5 6 Years after start of therapy

  5. Key Steps in Improving Treatment for Follicular Lymphoma Cure Prolongation of Life Palliation of Symptomes email@med.uni-muenchen.de

  6. Future Strategies in Follicular Lymphomas Therapy in Remission Induction Maintenance ASCT No further Therapy Chemotherapy plus Rituximab => Lymphoma Reduction => Lymphoma Control email@med.uni-muenchen.de

  7. FLIPI and Time to Treatment Failure low intermediate high

  8. 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

  9. Maintenance (SAKK) 1 dose q 2 months for 24 months follicular NHL stages III–IV, untreated • 6 x CHOP • 6 x FCM • 6 x COP • plus 8 x R R CR/PR Observation PDs/SDs off study PRIMA Study 2005 Follicular Lymphomas

  10. Maintenance (SAKK) 1 dose q 2 months for 24 months follicular NHL stages III–IV, untreated • 6 x CHOP • 6 x FCM • 6 x MCP • plus 8 x R R CR/PR Observation PDs/SDs off study OSHO/GLSG Study 2007 Follicular Lymphomas Not eligible for PBCT or Age > 65 Yrs. R

  11. FIT: 90Y-ibritumomab tiuxetan as first-line consolidation 90Y-ibritumomab tiuxetan (n=208) Newly diagnosed follicular lymphoma stage III/IV Induction chemotherapy* CRPR ** R watch & wait (n=206) NR PD off study R Randomisierung FIT: First-line Indolent lymphoma Trial * CVP, CHOP, Fludarabin (combination), etc. ** n = 414 Hagenbeek, ASH 2007;110: abstr 643

  12. FIT: 90Y-ibritumomab tiuxetan as first-line consolidation Progression-free survival Log rankp < 0.0001HR 0.463 90Y-ibritumomab tiuxetan:median 37 mo (n=208) Control: median 13.5 mo(n=206) Hagenbeek, ASH 2007;110: abstr 643

  13. GLSG Study `96 pts. < 60 yrs. (<65yrs.) 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. > 60 yrs. (>65 yrs.) 6 - 8 x CHOP intensive IFN-maintenance CR,PR standard IFN-maintenance Hiddemann et al., Blood 2005

  14. GLSG – Progression freeSurvival Lenz et al., Blood 2004

  15. 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. < 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. > 60 yrs IFN-maintenance 6 - 8 x CHOP

  16. 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. < 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. > 60 yrs IFN-maintenance 6 - 8 x CHOP

  17. 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

  18. 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

  19. 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 p<0.0001 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

  20. CHOP vs. R-CHOP +/-PBSCT 1524 patients randomized 156 not randomized 13 MRD data 861 first randomization 433 randomized R-CHOP 428 randomized to CHOP 553 assigned to R-CHOP 411 treated CHOP 418 treated R-CHOP 436 treated R-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

  21. p=0,0134 10 0 10 -1 10 -2 10 -3 MRD level 10 -4 10 -5 neg 74% 28% Diagnosis Induction 4 Induction 6 Induction 2 Quantitative t(14;18) AnalysisMRD levels at induction CHOP Induction p=0,0021 R-CHOP Induction p<0,0001 15% 28% 72%

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

  23. Remission Duration according to Consolidation MRD neg. MRD pos. UK SH

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

  25. 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“

  26. Key Steps in Improving Treatment for Follicular Lymphoma Cure Prolongation of Life Palliation of Symptomes email@med.uni-muenchen.de

  27. GLSG Study Group Supported by Deutsche Krebshilfe

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