Monday Night with Research To Practice: An 8-Part Live CME Webcast Series

1. Monday Night with Research To Practice: An 8-Part Live CME Webcast Series Part IV: Follicular LymphomaChronic Lymphocytic LeukemiaMonday, October 11, 20107:30 PM - 8:30 PM ET

2. Jonathan W Friedberg, MD, MMSc Associate Professor of Medicine and Hematology Chief, Hematology/Oncology Division James P Wilmot Cancer Center University of Rochester Rochester, New York Brad S Kahl, MD Associate Professor Director, Lymphoma Service University of Wisconsin School of Medicine and Public Health Associate Director for Clinical Research UW Carbone Cancer Center Madison, Wisconsin Neil Love, MDModerator Research To PracticeMiami, Florida

3. Disclosures for Moderator Neil Love, MD Dr Love is president and CEO of Research To Practice, which receives funds in the form of educational grants to develop CME activities from the following commercial interests: Abraxis BioScience, Allos Therapeutics, Amgen Inc, AstraZeneca Pharmaceuticals LP, Aureon Laboratories Inc, Bayer HealthCare Pharmaceuticals/Onyx Pharmaceuticals Inc, Biogen Idec, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Cephalon Inc, Eisai Inc, EMD Serono Inc, Genentech BioOncology, Genomic Health Inc, Genzyme Corporation, Lilly USA LLC, Millennium Pharmaceuticals Inc, Monogram BioSciences Inc, Myriad Genetics, Inc, Novartis Pharmaceuticals Corporation, OSI Oncology, Sanofi-Aventis and Spectrum Pharmaceuticals Inc.

4. Disclosures for Jonathan W Friedberg, MD, MMSc

5. Disclosures for Brad S Kahl, MD N/A = Not Applicable

6. Bendamustine Plus Rituximab Is Superior in Respect of Progression Free Survival and CR Rate When Compared to CHOP Plus Rituximab as First-Line Treatment of Patients with Advanced Follicular, Indolent, and Mantle Cell Lymphomas: Final Results of a Randomized Phase III Study of the StiL (Study Group Indolent Lymphomas, Germany).Rummel MJ et al. Proc ASH 2009;Abstract 405.Rituximab Maintenance for 2 Years in Patients With Untreated High Tumor Burden Follicular Lymphoma After Response to Immunochemotherapy. Salles GA et al. Proc ASCO 2010;Abstract 8004.Bortezomib, Bendamustine, and Rituximab in Patients with Relapsed or Refractory Follicular Lymphoma: Encouraging Activity in the Phase 2 VERTICAL Study.Fowler N et al. Proc ASH 2009;Abstract 933. Complete Response Rates With Lenalidomide Plus Rituximab for Untreated Indolent B-cell Non-hodgkin's Lymphoma.Fowler NH et al. Proc ASCO 2010; Abstract 8036.

7. Phase III Randomized Study of Bendamustine Compared With Chlorambucil in Previously Untreated Patients With Chronic Lymphocytic Leukemia.Knauf WU et al. J Clin Oncol 2009;27(26):4378-84. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: A randomised, open-label, phase 3 trial.Hallek M et al. Lancet 2010;376(9747):1164-74.Bendamustine Combined With Rituximab (BR) in First-line Therapy of Advanced CLL: A Multicenter Phase II Trial of the German CLL Study Group (GCLLSG).Fischer K et al. Proc ASH 2009;Abstract 205.

8. Case History: Dr Kahl • A 63-year-old woman with grade 1 stage IV follicular lymphoma • Asymptomatic • Maximum LN size 6 cm x 3 cm right iliac region • Bone marrow involvement with 10% FL cells • Normal LDH

9. 1) Would you recommend treatment for this patient at this time? Yes No

10. Case History: Dr Kahl (continued) • Patient declines treatment at this time • Followed q-3 months • Moderate progression over 1-year with fatigue and decreased stamina • Patient agrees to treatment now

11. 2) How would you treat the patient at this time? R-CVP/R-CHOP R-CVP/R-CHOP with maintenance rituximab R-bendamustine R-bendamustine with maintenance rituximab R-chemo followed by radioimmunotherapy Single-agent rituximab

12. Case History: Dr Kahl (continued) • Patient received R-CHOP and went into CR • Currently receiving maintenance rituximab

13. Follicular Lymphoma in the United States: First Report of the National LymphoCare Study Friedberg JW et al J Clin Oncol 2009;27(8):1202-8.

14. Initial Treatment in US: All Patients with Follicular Lymphoma Friedberg JW et al. JCO 2009; 27(8):1202-8.

15. National Patterns of Care Study with 43 US-Based Medical Oncologists: 186 Consecutive Patients with Newly Diagnosed FL

16. For a patient with newly diagnosed FL, what is currently your usual preferred up-front treatment? CI, Clinical Investigator; PO, Practicing Oncologist National Patterns of Care Survey of US Medical Oncologists, 9/2010

17. Rituximab Maintenance for 2 Years in Patients with Untreated High Tumor Burden Follicular Lymphoma After Response to Immunochemotherapy Salles GA et al. Proc ASCO 2010;Abstract 8004.

18. Effect on PFS with Rituximab Maintenance versus Observation in Phase III PRIMA Trial (N = 1,018) Salles GA et al. Proc ASCO 2010;Abstract 8004.

19. Do you currently use rituximab maintenance for patients receiving R-chemotherapy as front-line therapy for FL? CI, Clinical Investigator; PO, Practicing Oncologist National Patterns of Care Survey of US Medical Oncologists, 9/2010

20. Which of the following best describes how long you generally recommend that R maintenance be administered? CI, Clinical Investigator; PO, Practicing Oncologist National Patterns of Care Survey of US Medical Oncologists, 9/2010

21. Which of the following R maintenance regimens do you generally use? CI, Clinical Investigator; PO, Practicing Oncologist National Patterns of Care Survey of US Medical Oncologists, 9/2010

22. RESORT: Phase III Trial of Rituximab for Patients with Low Tumor Burden Indolent Non-Hodgkin’s Lymphoma (NHL) Estimated enrollment: 389 (closed) Stage III/IV NHL with low tumor burden treated with induction rituximab R Rituximab IV once a week for 4 weeks upon disease progression Rituximab IV once every 13 weeks until disease progression www.clinicaltrials.gov, October 2010.

23. Bendamustine Plus Rituximab versus R-CHOP as First-Line Treatment of Patients with Advanced Follicular, Indolent, and Mantle Cell Lymphomas: Final Results of a Randomized Phase III German Study Rummel MJ et al. ASCO/ASH Joint Session 2010; Abstract 405.

24. Efficacy Data: BR versus R-CHOP in Indolent Lymphomas Rummel MJ et al. ASCO/ASH Joint Session 2010.

25. Non-Hematologic Safety Data: BR versus R-CHOP Rummel MJ et al. ASCO/ASH Joint Session 2010.

26. When administering bendamustine ± rituximab for younger patients (≤65 years) with FL, what dose and schedule do you generally use? CI, Clinical Investigator; PO, Practicing Oncologist National Patterns of Care Survey of US Medical Oncologists, 9/2010

27. Erik Rupard, MDFort Gordon, GA In a patient with CD20-dim or negative FL, what is the role of rituximab as part of initial induction or as maintenance? Assuming this patient needs treatment, is rituximab-bendamustine the right choice?

28. Neal Fishbach, MDFairfield, CT Is ofatumumab-maintenance an option for a patient with FL who is in remission with front-line rituximab-bendamustine and has been having very severe hypersensitivity reactions with rituximab.

29. Case History: Dr Friedberg A 45-year-old woman presents with CVA and advanced stage FL R-CHOP x 6 R-maintenance x 2 years 1 year later, lung mass biopsy-confirmed recurrent Grade 1 FL Treated on study with VBR (bortezomib, bendamustine, rituximab) x 6

30. 3) Patient in remission after 6 cycles of VBR. How would you manage the patient at this time? Proceed with ASCT Refer for allo-SCT Observation Rituximab maintenance Bortezomib maintenance

31. Case History: Dr Friedberg (continued) • Patient observed and remains in remission two years after VBR therapy

32. Bortezomib, Bendamustine, and Rituximab in Patients with Relapsed or Refractory Follicular Lymphoma: Encouraging Activity in the Phase 2 VERTICAL Study Fowler N et al Proc ASH 2009;Abstract 933.

33. Response Rates with Bortezomib, Bendamustine and Rituximab (VBR) in Relapsed-Refractory FL: Phase II VERTICAL Study (N = 63) • 35% had high risk FLIPI at diagnosis • Patients had received a median of two prior therapies • 39% were refractory to their last rituximab-containing therapy Fowler N et al. Proc ASH 2009;Abstract 933.

34. Adverse Events in Relapsed-Refractory FL with Bortezomib, Bendamustine and Rituximab (VBR): Phase II VERTICAL Study Fowler N et al. Proc ASH 2009;Abstract 933.

35. Margaret Deutsch, MDRaleigh, NC What should be the preferred regimen for an octogenarian who has been previously treated with R-CVP for follicular lymphoma, and now needs re-treatment?

36. Case History: Dr Kahl An 82-year old man, with 10-year history of untreated CLL, develops B symptoms • WBC 300,000/mm3, Hb 9.0 g/dL, Platelets 95,000/mm3 • Bulky cervical adenopathy and palpable splenomegaly

37. 4) What other information is necessary at this time? Bone marrow evaluation CLL FISH panel CD38 status ZAP-70 status IgVH mutational status

38. Case History: Dr Kahl (continued) • A bone-marrow evaluation is done and shows diffuse involvement of bone-marrow with CLL (80% of marrow) • FISH panel reveals del11q and trisomy 12

39. 5) How would you treat this patient? Chlorambucil Fludarabine Bendamustine Rituximab-bendamustine FCR FR Other

40. What is your usual preferred initial regimen for a patient with CLL requiring treatment? CI, Clinical Investigator; PO, Practicing Oncologist National Patterns of Care Survey of US Medical Oncologists, 9/2010

41. Addition of Rituximab to Fludarabine and Cyclophosphamide in Patients with Chronic Lymphocytic Leukaemia: A Randomised, Open-Label, Phase III Trial Hallek M et al. Lancet 2010;376(9747):1164-74.

42. Impact of FCR on Overall Survival in CLL Hallek M et al. Lancet 2010;376(9747):1164-74.

43. Efficacy and Safety of Oral Fludarabine Phosphate in Previously Untreated Patients With Chronic Lymphocytic Leukemia Rossi JF et al. J Clin Oncol 2004;22(7):1260-7.

44. Efficacy and Safety of Oral Fludarabine (N = 81) Rossi JF et al. J Clin Oncol 2004;22(7):1260-7.

45. Low-Intensity Fludarabine, Cyclophosphamyde, Rituximab (FCR) as Front-Line Treatment for Follicular Lymphoma. Efficacy and Toxicity Profile of the Oral Versus Intravenous Administration Marin-Niebla A et al. Proc ASH 2009;Abstract 2690.

46. Efficacy and Safety of FCR IV versus FCR Orally Administered (N = 86) Marin-Niebla A et al. Proc ASH 2009;Abstract 2690.

47. Richard Polkinghorn, MDBrunswick, ME For a patient with newly diagnosed CLL with an adverse FISH panel, would the choice of initial induction be different than if the patient did not have the adverse marker?

48. Neal Fishbach, MDFairfield, CT Where do we place ofatumumab in the treatment algorithm of CLL?

49. Dr. Steven Paul, MD, PhD When would you treat a patient with CLL, no symptoms, slightly enlarged spleen, not palp node; WBC 19,000 with 70% lymphs, nl platelets, and Hgb of 11? Patient has an 85% ZAP 70 score.