Autologous SCT in FL No!

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1 COSTEM 2011 Controversies in Stem Cell Transplantation and Cellular Therapies Berlin, September 10 th, 2011 Autologous SCT in FL No! Ulrich Dührsen Department of Hematology

2 Follicular lymphoma Positioning of autologous stem cell transplantation Diagnosis 1st line therapy Relapse Transformation

3 Follicular lymphoma Positioning of autologous stem cell transplantation Diagnosis 1st line therapy Relapse Transformation

4 First line therapy of follicular lymphoma Current standard: 6 cycles R-chemo + R maintenance Progression-free survival Overall survival ORR 94% 3-yr PFS ~ 75 % 3-yr OS > 90 % (n=1018) Salles et al, Lancet 377: 42, 2011

5 First line therapy of follicular lymphoma Conventional versus high-dose therapy PFS / EFS Lenz et al, yr PFS ~ 70 % Sebban et al, yr EFS ~ 50 % (n=240) (n=401) Deconinck et al, yr EFS ~ 70 % Ladetto et al, yr EFS ~ 65 % (n=166) (n=134)

6 First line therapy of follicular lymphoma Conventional versus high-dose therapy PFS / EFS GLSG, yr PFS ~ 80 % Sebban et al, yr EFS ~ 50 % (n=300) (n=401) Deconinck et al, yr EFS ~ 70 % Ladetto et al, yr EFS ~ 65 % (n=166) (n=134)

7 First line therapy of follicular lymphoma Conventional versus high-dose therapy OS Lenz et al, yr OS ~ 90 % Sebban et al, yr OS ~ 85 % (n=240) (n=401) Deconinck et al, yr OS ~ 90 % Ladetto et al, yr OS ~ 85 % (n=166) (n=134)

8 First line therapy of follicular lymphoma Conventional versus high-dose therapy toxicity Lenz et al, yr saml/mds ~ 4 % Sebban et al, 2006 No increased late toxicity saml/mds Solid Tumors CHOP-HDT (192) 2 9 CHVP-IFN (209) 4 10 Gyan et al, yr secondary cancers ~ 15 % Ladetto et al, yr smds ~ 7 %

9 First line therapy of follicular lymphoma Conventional versus high-dose therapy financial burden Conventional therapy 6 cycles R-CHOP High-dose therapy + ASCT 3 cycles R-CHOP stem cell mobilisation autologous transplantation Total

10 First line ASCT in follicular lymphoma No! First line autologous SCT in FL - improves PFS in comparison to old standard therapies - has not been shown to improve PFS in comparison to current standard therapy - has no positive impact on OS - causes significant short-term and long-term toxicity - is twice as costly as conventional therapy

11 Follicular lymphoma Positioning of autologous stem cell transplantation Diagnosis 1st line therapy Relapse Transformation

12 Therapy of relapsed follicular lymphoma Current standard: 6 cycles R-chemo + R maintenance Progression-free survival Overall survival ORR 85% 3-yr PFS ~ 50 % 3-yr OS ~ 75 % (n=334) Van Oers et al, Blood 108: 3295, 2006 and J Clin Oncol 28: 2853, 2010

13 Therapy of relapsed follicular lymphoma Conventional versus high-dose therapy the CUP trial Progression-free survival Overall survival ORR 75% 3-yr PFS ~ 45 % 3-yr OS ~ 60 % Schouten et al, J Clin Oncol 21: 3918, 2003

14 Therapy of relapsed follicular lymphoma Conventional versus high-dose therapy retrospective data Event-free survival Overall survival 3-yr EFS ~ 75 % 3-yr OS ~ 90 % ASCT No ASCT (n=153) Le Gouill et al, Haematologica 96: 1128, 2011

15 Therapy of relapsed follicular lymphoma High-dose therapy ± rituximab retrospective data Event-free survival Overall survival 3-yr EFS ~ 75 % 3-yr OS ~ 90 % (n=98) Sebban et al, J Clin Oncol 26: 3614, 2008

16 Follicular lymphoma Positioning of autologous stem cell transplantation Diagnosis 1st line therapy Relapse Transformation

17 Therapy of transformed follicular lymphoma Current standard: R-chemotherapy? Overall survival 3-yr OS ~ 35 % (n=170) Al-Tourah et al, J Clin Oncol 26: 5165, 2008

18 Therapy of transformed follicular lymphoma Current standard: High-dose therapy with autologous SCT? 3-yr OS ~ 60 % Williams et al, J Clin Oncol 19: 727, 2001

19 Retrospective high-dose therapy studies Selection of the best Relapse ± transformation Conventional therapy High-dose therapy Resistant disease No stem cells Poor condition Definitive treatment

20 Therapy of transformed follicular lymphoma A prospective trial Conventional therapy SD / PD High-dose therapy CR / PR 3-yr OS ~ 20 % 3-yr OS ~ 70 % Eide et al, Br J Haematol 152: 600, 2011

21 ASCT for relapsed or transformed FL No! Relapsed FL - current standard therapy is very efficient - autologous SCT has not been shown to improve survival in comparison to current standard therapy - patient selection obscures treatment results - significant short-term and long-term toxicities, financial burden Transformed FL - scanty data!

22 FLiRT trial Follicular Lymphoma in Relapse or Transformation conventional versus intensified therapy Refraktäres, rezidiviertes oder transformiertes follikuläres Lymphom, Grad 1 oder 2 Ein- / Ausschlusskriterien, histologische Sicherung, Staging B S Relapsed or transformed follicular lymphoma 2 x R-CHOP / R-ICE Dokumentationsbögen (Bögen S, R und F stets mit Lebensqualitätserhebung EORTC-QLQ-C30) T I N D U K T I O N _ 1 x R-CHOP / R-ICE S t a m m z e l l a p h e r e s e + R a n d o m i s a t i o n 1 x R-CHOP / 1 x R-CHOP / R-ICE R-ICE AR AR T 3 x R-CHOP / R-ICE 3 x R-CHOP / R-ICE KONSOLIDIERUNG ERHALTUNG Restaging Restaging Restaging PD CR, PR, SD 3 x R-CHOP / R-ICE 3 x R-CHOP / R-ICE 3 x R + 1 x BEAM + Auto-Tx CR, PR, SD A b s c h l u s s s t a g i n g PD CR, PR, SD Rituximab-Erhaltungstherapie vierteljährlich über 2 Jahre (8 Gaben) T h e r a p i e e n d e - N a c h s o r g e Therapieversagen Freie Therapie R T R T F F 3 x R-CHOP / R-ICE 3 x R + BEAM/ASCT Arm 0 Arm A Arm B Nicht-random. Randomisierter Studienteil R maintenance for 2 years