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Lymphoma Update 2013: Treatment Strategies and New Perspectives

Explore the latest advancements and treatment options for lymphomas, including follicular lymphoma and Hodgkin’s lymphoma. Learn about chemotherapy combinations and targeted therapies to improve outcomes and patient survival rates.

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Lymphoma Update 2013: Treatment Strategies and New Perspectives

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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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