Evolving Therapies for Elderly Patients with Blood Cancers

1. Evolving Therapies for Elderly Patients with Blood Cancers Andrew Artz, MD, MS Associate Professor of Medicine Clinical Director, Hematopoietic Cellular Therapy Program

2. Background • New diagnostic tools • New Drugs • Blood and Marrow Transplant • Outline Presentation Title Here |

3. Growth of Older Population: US Census Data Centenarians (100+): Account for 1.7% of population in 2010 United States Census Data Presentation Title Here |

4. Blood Cancers Mostly Occur in Older Adults Lymphoma CLL and others AML, MDS and others Milena Sant et al. Blood 2010;116:3724-3734 Presentation Title Here |

5. Personalized Medicine: New Diagnostics and Treatment Presentation Title Here |

6. Immunotherapy: “Checkpoint blockade” Nivolumab and pembrolizumab are examples Presentation Title Here |

7. Tailor Therapy to Fitness or “Physiologic Age” Presentation Title Here |

8. New Approvals • Antibodies. Obinutuzumab* (gazyva), and ofatumumab* (arzerra) • Targeted oral drugs: Ibrutinib (imbruvica), idelalisib* (zydelig), venetoclax (venclexta) • Exciting • Targeted BTK acalabrutinib with 95% response rate in previously treated pts • CART cells • CLL Presentation Title Here |

9. New Approvals. None. Fast tracked FDA • Midostaurin (AML with FLT-3) + chemo in younger pts. Average survivals 6 years vs 2 years without drug • Exciting • Targeted drugs for FLT-3, IDH • New antibody drugs again CD25, CD47, CD33 • AML Presentation Title Here |

10. New approvals • HiDAC inhibitor. Panobinostat* (farydak) • Proteosome inhibitor: Ixazomib* (ninlaro), carfilzomib* (kyprolis) • Monoclonal antibodies. Elotuzumab* (Empliciti), daratumumab (darzalex) • Exciting • Proof of above therapies • checkpoint inhibitors • autotransplant plus therapy before and after • Multiple Myeloma Presentation Title Here |

11. New approval. Blinatumomab (CD19+). 80% response for previously treated disease. • Exciting • CAR-T cells • Blinatumomab with initial treatment • Inotuzumab(ALL with CD22+) • Acute Lymphoblastic Leukemia Presentation Title Here |

12. For CML • Around 50% can stop drugs without return over 2 years • Combination of drugs to get deeper response • Atypical CML/CNL. Rare type with CSF3R can respond to ruxolitinib or dasatinib. • Chronic Myeloid Leukemia (CML) Presentation Title Here |

13. MDS: No drug approvals! • New Treatments • Rigosertib plus azacitidine. 84% responded (only 37 pts) • Luspatercept improved anemia around 80% • Aplastic anemia. Addition of eltrombopag, a platelet growth factor had high response combined with standard therapy • MDS and Aplastic Anemia Presentation Title Here |

14. Buyer beware of “cures”! Presentation Title Here |

15. Many different targets! Gerberg, DE, Americal Family Physician: 2008:(3) Transplant in Older Adults

16. Trends in Allogeneic Transplants by Recipient Age*

17. Trends in Allogeneic HCT Utilization for Adults ≥70 Years, by Disease Absolute No. HCTs ≥70 Years

18. From Prognosis to Optimization: Transplant Optimization Program (TOP) for Older Adults Interdisciplinary Meeting Transplant in Older Adults

19. Summary • Personalized medicine is here. Each cancer and patient requires different treatment • New drugs and immune therapy are improving success • For fit older patients, transplant often an option Presentation Title Here |