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Rare diseases with no satisfying standard treatment Lack of randomised phase III trials

„It´s Time to Take Care of T-Cell Lymphomas“ Autologous Stem Cell Transplantation in Peripheral T-Cell Lymphoma (PTCL) Peter Reimer , University of Würzburg, Germany Bologna, October 24 th 2006. Long-term survival (%). Overall survival (%). Time (months). Gisselbrecht et al. Blood (1998).

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Rare diseases with no satisfying standard treatment Lack of randomised phase III trials

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  1. „It´s Time to Take Care of T-Cell Lymphomas“Autologous Stem Cell Transplantation in Peripheral T-Cell Lymphoma (PTCL)Peter Reimer, University of Würzburg, GermanyBologna, October 24th 2006

  2. Long-term survival (%) Overall survival (%) Time (months) Gisselbrecht et al. Blood (1998) Autotransplantation in PTCL - Rationale • Rare diseases with no satisfying standard treatment • Lack of randomised phase III trials • Poor results following conventional (anthracycline-based) chemotherapy

  3. Autotransplantation in PTCL-NOS - Rationale CENSOR FAIL TOTAL MEDIAN 21 27 48 3.5 63 148 211 1.95 Failure-free survival Overall Survival 1.0 1.0 0.8 0.8 p=<0.001 p=0.0076 0.6 0.6 Proportion Proportion 0.4 0.4 0.2 0.2 0.0 0.0 0 2 4 6 8 10 12 14 16 18 0 2 4 6 8 10 Time Time HD Therapy Transplantation CENSOR FAIL TOTAL MEDIAN 1. line 8 15 23 1.46 yes no 2. line 0 24 24 0.71 Vose et al. ASH (2005)

  4. Anaplastic Large Cell Lymphoma Anaplastic Lymphoma Kinase (ALK) Kutok et Aster JCO (2002) Kutok et Aster JCO (2002)

  5. Anaplastic Large Cell Lymphoma probability Falini et al. Blood (1999) Falini et al. Blood (1999) → ALK+ ALCL no candidate for primary autoSCT

  6. Autotransplantation in PTCL – Salvage Treatment Retrospective data

  7. Autotransplantation in PTCL – Salvage Treatment Retrospective data

  8. Autotransplantation in PTCL – Salvage Treatment • Only retrospective data Complete response rate ≈ 60% Long-term overall survival rate ≈ 30-50% → Autotransplantation seems a reasonable treatment approach in relapsing/refractory PTCL

  9. Autotransplantation in PTCL – 1. Line Treatment Retrospective Prospective* * No PTCL-restricted trials, subgroup analyses

  10. Autotransplantation - 1. Line Treatment Prospective Trials PTCL • Inclusion criteria • Age 18-65 years • PTCL except ALK+ ALCL, CTCL • ECOG < 3 • Informed consent • No severe uncontrolled comorbidities 4 (-6) x CHOP PR/CR DexaBEAM/ESHAP PR/CR Stem Cell Collection High-Dose Cyclophosphamid (60mg/kgKG) + TBI Auto SCT Reimer et al. Hematol J (2004)

  11. Autotransplantation - 1. Line Treatment Prospective Trials Histology (n= 30) NOS AILT ALK- ALCL Other Reimer et al. Hematol J (2004)

  12. Autotransplantation - 1. Line Treatment Prospective Trials Patient characteristics (n=30) Reimer et al. Hematol J (2004)

  13. Autotransplantation - 1. Line Treatment Prospective Trials Overall Survival Median follow-up 15 months Reimer et al. Hematol J (2004)

  14. Acute Toxicity HDT CHOP Reimer et al. Hematol J (2004)

  15. Toxicity • Treatment-related mortality (TRM) • - 3% of pats. died due to infectious complications / multi- organ deficiency • → acute TRM similar to high-dose studies in aggressive (B-cell) lymphomas • Late toxicity • - 2 patients developed MDS/AML • (1 pat. died of AML, 1 pat. is in CR following allogeneic stem cell transplantation)

  16. Autotransplantation - 1. Line Treatment Prospective Trials • Inclusion criteria • Age 18-60 years • PTCL stage II-IV, except CTCL • HIV, Hep. B/C negative • Informed consent • No severe uncontrolled comorbidities PTCL PTCL MACOP-B 2xAPO 2x DHAP HD AraC/Mito Cycl/Cispl, Etop Stem Cell Collection HD Melph/Mito BEAM AutoSCT Corradini et al. Leukemia (2006)

  17. Autotransplantation - 1. Line Treatment Prospective Trials Patient characteristics (n=62) NOS AILT ALK+ ALCL ALK- ALCL Intestinal Corradini et al. Leukemia (2006)

  18. Autotransplantation - 1. Line Treatment Prospective Trials OS DFS Median follow-up 76 months Corradini et al. Leukemia (2006)

  19. Autotransplantation - 1. Line Treatment Prospective Trials 50% 40% OS (n=62) OS (n=75) OS non-ALCL alk+ Ovarell survival (%) Time (months) Corradini et al. Leukemia (2006) Reimer German Trial updated 10/2006

  20. Autotransplantation - 1. Line Treatment Prospective Trials Phase II studies * Non ALK+ ALCL

  21. Autotransplantation - 1. Line Treatment Prognostic Factors Corradini et al. Leukemia (2006)

  22. Autotransplantation - 1. Line Treatment Prognostic Factors aaIPI Response rate (%) PD under CHOP (%) Relapse after autoSCT (n) Reimer et al. ASH (2005)

  23. Conclusions • Autotransplantation as primary treatment in PTCL is feasible. Toxicity is similar to aggressive B-cell lymphomas. • However, about 30% of patients do not achieve autotransplantation mainly due to progressive disease. • Long-term DFS is best for patients achieving CR before ASCT • Autotransplantation in relapsing/refractory PTCL shows results comparable to aggressive B-cell lymphomas and should be considered in this situation. • Data need to be validated in randomised studies.

  24. Planned Phase III Trials DHAP CHOEP 14 CHOEP 14 CHOEP 14 CHOEP 14 CHOEP 14 CHOEP 14 CHOEP 14 CHOEP 14 CHOEP 14 CHOEP 14 CHOEP 14 CHOEP 14 DHAP CHOEP 14 A-CHOEP 14 A-CHOEP 14 CHOEP 14 A-CHOEP 14 CHOEP 14 CHOEP 14 A-CHOEP 14 CHOEP 14 A-CHOEP 14 A-CHOEP 14 CHOEP 14 German Group Auto SCT FLU 125 /m2 BUS 12 /kg CYC 120 /kg R Allo SCT FLU 125 /m2 BUS 12 /kg CYC 120 /kg Nordic Group Auto SCT BEAM R Allo SCT BEAM

  25. PTCL Study – Attending Centers

  26. Back up

  27. Outcome Relapse CR/PR Other PD n= 85 PTCL n= 24 n= 42 n= 19 Under therapy ASCT No ASCT n= 18 n= 6 n= 29 n= 11 n= 2 Other Reimer, ASH 2005

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