1. Targeting BTK Signaling in B-Cell Malignancies

2. This program will include a discussion of off-label treatment and investigational agents not approved by the FDA for use in the US, and data that were presented in abstract form. These data should be considered preliminary until published in a peer-reviewed journal.

3. BTK as a Target in B-Cell Malignancies

4. Outcomes With Ibrutinib in Patients With R/R CLL by Chromosomal Abnormality and Karyotype

5. RESONATE: Ibrutinib vs Ofatumumab in Patients With Previously Treated CLL

6. RESONATE-2 Study Design

7. RESONATE-2 Patient Characteristics

8. RESONATE-2 Efficacy and Safety Outcomes

9. PFS by Prior Lines of Therapy RESONATE and RESONATE-2

10. Phase 2 Study of Ibrutinib in MCL

11. RESONATE Disposition and Treatment Exposure With Ibrutinib

12. OSU Experience Long-Term Ibrutinib in CLL

13. Predictors of Ibrutinib Discontinuation OSU Experience

14. Ibrutinib Resistance Mutations

15. Molecular Model of Ibrutinib Resistance

16. Real-World Discontinuation Rates with Ibrutinib

17. Toxicities Most Commonly Causing Ibrutinib Discontinuation in Real-World Setting

18. Real-World Efficacy Outcomes with Ibrutinib

19. Ibrutinib-Related Bleeding Across Trials

20. Anticoagulation and Ibrutinib-Related Bleeding

21. AF Incidence Over Time on Ibrutinib

22. Risk Factors for AF in Ibrutinib RCTs

23. Ibrutinib and VAs?

24. Maintain Awareness for VA

25. Practical Issues When Initiating Ibrutinib Drug-Drug Interactions

26. Screening Patients With Cardiac Risk

27. Ibrutinib Has Many Off-Target Effects

28. Acalabrutinib (ACP-196)

29. ACE-CL-001 Acalabrutinib Monotherapy in R/R CLL

30. ACE-CL-001 Outcomes

31. ELEVATE CLL R/R: Acalabrutinib vs Ibrutinib in Previously Treated High-Risk CLL

32. Acalabrutinib in MCL

33. Next-Generation BTK Inhibitors Zanubrutinib (BGB-3111)

34. Next-Generation BTK Inhibitors GS-4059 (ONO-4059)

35. Vecabrutinib (SNS-062) Activity Does Not Require C481

36. Key Takeaways

37. Abbreviations

38. Abbreviations (cont)

39. Abbreviations (cont)