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2013 Lymphoma Update

2013 Lymphoma Update. 2013.08.05. Outline. Follicular lymphoma Hodgkin’s lymphoma Chronic lymphocytic leukemia. Follicular Lymphoma. Epidemiology of FL. Account 22% of NHL Chronic relapsing and remitting pattern Most patients aged > 50 Median survival 12~14 years.

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2013 Lymphoma Update

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  1. 2013 Lymphoma Update 2013.08.05

  2. Outline • Follicular lymphoma • Hodgkin’s lymphoma • Chronic lymphocytic leukemia

  3. Follicular Lymphoma

  4. Epidemiology of FL • Account 22% of NHL • Chronic relapsing and remitting pattern • Most patients aged > 50 • Median survival 12~14 years

  5. 1st line treatment in FL R-CVP vs CVP 4-yr OS 83% vs 77% (P=0.0290) R-CHOP vs CHOP 2-yr OS 95% vs 90% (P=0.016) Blood 2005;106:3725 Lancet 2013;381:1203

  6. There’s still a role for watch& wait, despite new therapy modalities Combined immuno-chemotherapy is standard of care Rituximab maintenance as consolidation Which chemotherapy should be best combined with Rituximab? Standard care with indolent lymphoma New perspectives

  7. B-R vs R-CHOP StiL NHL 1-2003 R 81 centers in Germany Enrolled between Sep 2003~Aug 2008 Stage III/IV IL or MCL Median f/u 45 mos Non-inferiority study Primary endpoint: PFS Rummel et al. Lancet 2013;381:1203

  8. Grade 3+4 hematotoxicity Non-hematological toxicity Rummel et al. Lancet 2013;381:1203

  9. Response rates Rummel et al. Lancet 2013;381:1203

  10. PFS Rummel et al. Lancet 2013;381:1203

  11. MCL FL Marginal zone Waldenstrom Rummel et al. Lancet 2013;381:1203

  12. Conclusion • B-R is not only less toxic but also more effective than R-CHOP • B-R could be considered as a preferred 1st-line treatment for patients with FL, indolent and MCL Rummel et al. Lancet 2013;381:1203

  13. Treatment strategies in IL Immunochemotherapy Maintenance Tumor reduction Eradication?

  14. PRIMA: study design

  15. PFS Lancet 2010;377:42

  16. OS Lancet 2010;377:42

  17. Lancet 2010;377:42

  18. B-R with maintenance StiL NHL 7-2008 MAINTAIN R Induction with B-R If CR or PR then maintenance Primary endpoint: PFS Rummel et al. Lancet 2013;381:1203

  19. Hodgkin’s lymphoma

  20. HL is a curable disease Significant improvement in survival rate between 1970s and 1990s; However, the survival rate has plateaued in last two decades BEACOPP MOPP Stanford V GHSG HD9 study 1995 1980 2009 1992 ABVD 5-year survival of HL still is only 85%

  21. ABVD or BEACOPP? JCO 2013;31:684 Lancet 2012;379:1791

  22. Different approaches to targeting CD30

  23. CD30-directed immunotherapy

  24. Brentuximab vedotin antibody-drug conjugate (ADC)

  25. Mechanism of Brentuximab vedotin

  26. Phase II trial of brentuximab vendotin in R/R HL Eligilibilty Treatment (n=102) Follow-up Primary endpoint: ORR by Independent review Facility (IRF) JCO 2012;30:2183

  27. JCO 2012;30:2183

  28. JCO 2012;30:2183

  29. Summary: changing therapeutic paradigms? • ABVD • BEACOPP Standard treatment Open questions Improving salvage? Introducing maintenance? 1st line New combination?

  30. GHSG approach:“targeted BEACOPP” BrECADD Study is recruiting since 2012/11

  31. Chronic lymphocytic leukemia

  32. Classification of CLL patients according to their fitness Blood 2009;114:3359

  33. History of anti-CD20 mAbs

  34. GA 101: type II, glycoenginered anti-CD20 mAb • First type II, glycoengineered , humanized IgG1 anti-CD 20 mAb • In preclinical studies comparing against rituximab, GA 101 provided: • Enhanced ADCC, oligosaccharides that enhance the interaction with FcγR, particularly FcγRIIIa, even in effector cells bearing the low affinity polymorphic variant of FcγRIIIa • Increased direct cell death induction • Decreased complement-dependent cytotoxicity

  35. Type I and type II anti-CD20 mAbs

  36. Summary of direct cell death with type II mAbs (GA 101) • Most anti-CD20 mAbs in development are type I. Non of type I mAbs had proven to be superior to rituximab. • The type II anti-CD20 mAb GA101 exhibit increased PCD, enhanced ADCC and lower CDC compared with type I mAbs • GA 101 induced PCD via non-apoptotic pathways involving lysosomes nad ROS • Loss of cell surface CD20 by ”shaving” involving phagocytosis and modulation on tumor surface may affect anti-CD20 efficacy of mAbs.

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