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GHSG Risk groups

GHSG Risk groups. Early favorable stages: CS I/II without risk factors* Early unfavorable stages: CS I/II with risk factors* Advanced stages: CS III/IV; selected CS IIB. *a) large mediastinal mass; b) extranodal disease; c) high ERS; d) 3 or more areas. Hodgkin Lymphoma

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GHSG Risk groups

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  1. GHSG Risk groups Early favorable stages: CS I/II without risk factors* Early unfavorable stages: CS I/II with risk factors* Advanced stages: CS III/IV; selected CS IIB *a) large mediastinal mass; b) extranodal disease; c) high ERS; d) 3 or more areas

  2. Hodgkin Lymphoma Historical prognosis of patients in advanced stages 100 80 60 Alkylating agents (1965) 40 20 No therapy (1940) 0 0 1 2 3 4 5 Years

  3. Long-term results for HL patients in advanced stages FFTF OS Years after study entry Canellos et al NEJM 2002

  4. BEACOPP baseline (base) and escalated (esc) Drug base2 esc2 route schedule Bleomycin 10 10 iv 8 Etoposide 100 200 iv 1-3 Adriamycin 25 35 iv 1 Cyclophosphamide 650 1250 iv 1 Vincristine 1.41 1.41 iv 8 Procarbazine 100 100 po 1-7 Prednison 40 40 po 1-14 G-CSF - + sc 8-14 1max. 2,0 mg 2mg/m2

  5. HD9 study for advanced stages (1994-98; 1195) Design CS IIB-IIIA with RF CS IIIB; CS IV Arm A 8 x (COPP/ABVD) ± RT Arm B 8 x BEACOPP baseline ± RT Arm C 8 x BEACOPP escalated ± RT RT on initial bulk and residual disease Diehl et al NEJM 2003

  6. 1.0 A (n=260) 0.9 B (n=469) 0.8 C (n=466) 0.7 Probability 0.6 Median observation time : 86 months 0.5 p<0.0001 A vs. B: p=0.090 A vs. C: p<0.0001 B vs. C: p<0.0001 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 FFTF (years) HD9 Update (7-year follow-up) FFTF At 7 years : Arm A 67%; Arm B 75%; Arm C 85%

  7. A (n=260) B (n=469) C (n=466) HD9 Update (7-year follow-up) OS 1.0 0.9 0.8 0.7 Probability 0.6 0.5 p=0.0042 A vs. B: p=0.17 A vs. C: p<0.0001 B vs. C: p=0.034 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 OS (years) At 7 years : Arm A 79%; Arm B 84%; Arm C 90%

  8. HD9 trial of the GHSG: 7 year follow-up 7-year failure rates by IPS (%) Arm A Arm B Arm C IPS 0 - 1 22 17 9 IPS 2 - 3 36 27 17 IPS 4 - 7 41 26 19 Treatment failure rates (5-year Kaplan-Meier) GHSG 2001 HD9

  9. Hodgkins LymphomaLate side effects after initial treatment • 2nd NPL AML • NHL • Solid tumours • Organ damage Lung • Heart • Thyroid • Others Fertility • OPSI • Fatigue • Psycho-social

  10. CS IIB with RF a,b; CS III and IV 8x BEACOPP escalated EPO/Placebo 6x BEACOPP escalated EPO/ Placebo 8x BEACOPP 14 EPO/Placebo Restaging PR; res dis >2.5 cm No Yes Risk factors: Large mediastinal mass b) Extranodal disease PET - PET + Follow-up GHSG ongoing study for advanced stages (HD15) 30 Gy RX on res disease Follow-up

  11. PET in Hodgkin patients with residual mediastinal mass Patient A Patient B

  12. PET used for early prognostic assessment in HL Comparison PET/CT after 2xABVD Hutchings et al, Blood 2005

  13. Proposed GHSG HD18 trial for advanced HLDesign 2 x BEACOPP escalated PET + PET - 6xBEACOPPesc 6xR-BEACOPPesc 6xBEACOPPesc 2xBEACOPPesc End of therapy: PET; RX to res nodes > 2.5 cm Neg: Follow up

  14. Treatment of advanced-stage HL Summary BEACOPPescalated better than COPP/ABVD (FFTF 18%; OS 11%) at 7 years BEACOPPescalated better than BEACOPPbaseline (FFTF 10%; OS 6%) at 7 years No overall difference in 2nd NPL; sAML <1% in HD12 BEACOPPescalated standard in follow-up studies PET used as prognostic indicator in future trials (HD18)

  15. Treatment of Hodgkin Lymphoma • Background • First-line treatment • Treatment of relapse • Summary

  16. GHSG 1988 - 1999 (n = 513; total: 3809) 1.0 .8 .6 late relapse 52/169 Probability early relapse 64/138 .4 primary progressive 129/206 p <0.0001 .2 0.0 0 12 24 36 48 60 72 84 96 108 120 Overall survival (months) Prognosis of patients with relapsed HL after first-line chemotherapy Josting et al JCO 2000

  17. European multicentre study for patients with relapsed Hodgkins Lymphoma (HD-R2) RA N D O M I S A T I O N RE G I S T R I E R U N G DHAP DHAP BEAM PBSC DHAP DHAP CTX MTX VP16 BEAM

  18. 1.0 0.9 0.8 0.7 0.6 Probability OS 0.5 FFTF 0.4 0.3 Median observation 18 months OS 87% FFTF 71% 0.2 0.1 0.0 0 6 12 18 24 30 36 Time (months) HD-R2 study for patients with relapsed HL 2nd interim analysis

  19. Hodgkin LymphomaImmunohistology

  20. Clinical trials with MoAb-based constructsin patients with refractory HL (Selection) Construct Target Patients Response (n) (%) Immunotoxin1) CD25 15 14 Immunotoxin2) CD30 17 7 Bi-MoAb3) CD30x64 10 40 RadioIT4) CD30 22 27 Rituximab5) CD20 18 89 1)Engert Blood 1997; 2)Schnell Clin Cancer Res 2002; 3)Borchmann Blood 2003; 4)Schnell JCO 2005; 5)Schulz Blood 2003

  21. Treatment of Hodgkin Lymphoma • Background • First-line treatment • Treatment of relapse • Summary

  22. Current treatment of Hodgkin Lymphoma (GHSG) • 2xABVD plus IF radiotherapy standard in early favorable stages • 4xABVD plus IF radiotherapy standard in early unfavorable stages • 8xBEACOPPescalated standard in advanced stages • High-dose chemotherapy for pts with relapse • Need better definition of individual risk profiles (PET) and reduction of long-term toxicity • Development of immunotherapy ongoing

  23. German Hodgkin Study Group (GHSG) Chairman: V. Diehl Secretary: A. Engert Pathology: K. Müller-Hermelink, H. Stein M. Hansmann Radiotherapy: R.-P. Müller, H. Eich PET Panel: M. Dietlein KKSK : U. Paulus, B. Pfistner Physicians: P. Borchmann, A. Josting, D. Re H. Bredenfeld, B. Klimm, K. Behringer, M. Fuchs Documentation: H. Nisters-Backes, B. Hoffmann

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