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Handling Bad News: How to Best Manage TP53 Myeloid Disease

Program: Education Program
Hematology Disease Topics & Pathways:
Genomics, Diseases, Treatment Considerations, Biological therapies, Myeloid Malignancies, Biological Processes, Transplantation (Allogeneic and Autologous)
Saturday, December 7, 2024: 4:00 PM-5:15 PM
Grand Hall D (Manchester Grand Hyatt San Diego)

Description:
Mutations of TP53 are present in 10-15% of cases of de novo acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and approximately 30% of cases of therapy-related myeloid neoplasms. TP53-mutated myeloid disease is associated with complex cytogenetic abnormalities and poor outcome, with a median survival of only 5-10 months. In this educational session, we will explore the impact of TP53 mutation type and number on outcomes and clinical management.  We will review current and emerging treatment approaches for this high-risk subtype of AML/MDS.

Dr. Daniel Link will discuss evidence that TP53 hotspot mutations have dominant negative or gain-of function properties and discuss the potential impact on outcome and clinical management. He will review recent data establishing the importance of determining TP53 mutant allele status (monoallelic versus multi-hit). 

Dr. Marina Konopleva will review current non-transplant therapeutic approaches for TP53-mutated myeloid disease and discuss new therapies on the horizon, including chimeric antigen receptor therapies, mutated p53 reactivators, Fc fusion protein and monoclonal antibodies targeting various myeloid antigens.

Dr. Hugo Fernandez will discuss the use of allogenic hematopoietic transplant in the treatment of TP53-mutated myeloid disease, including new approaches to tailor conditioning and use maintenance therapy after transplantation.

Chair:
Daniel C Link, MD, Washington University School of Medicine in St. Louis
Disclosures:
No relevant conflicts of interest to declare.

Mutations of TP53 are present in 10-15% of cases of de novo acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and approximately 30% of cases of therapy-related myeloid neoplasms. TP53-mutated myeloid disease is associated with complex cytogenetic abnormalities and poor outcome, with a median survival of only 5-10 months. In this educational session, we will explore the impact of TP53 mutation type and number on outcomes and clinical management.  We will review current and emerging treatment approaches for this high-risk subtype of AML/MDS.

Dr. Daniel Link will discuss evidence that TP53 hotspot mutations have dominant negative or gain-of function properties and discuss the potential impact on outcome and clinical management. He will review recent data establishing the importance of determining TP53 mutant allele status (monoallelic versus multi-hit). 

Dr. Marina Konopleva will review current non-transplant therapeutic approaches for TP53-mutated myeloid disease and discuss new therapies on the horizon, including chimeric antigen receptor therapies, mutated p53 reactivators, Fc fusion protein and monoclonal antibodies targeting various myeloid antigens.

Dr. Hugo Fernandez will discuss the use of allogenic hematopoietic transplant in the treatment of TP53-mutated myeloid disease, including new approaches to tailor conditioning and use maintenance therapy after transplantation.

Daniel C Link, MD

Siteman Cancer Center, Washington University School of Medicine in St. Louis, Saint Louis, MO

Marina Konopleva

Albert Einstein College of Medicine, Houston, TX

Hugo Francisco Fernandez, MD

Moffitt Malignant Hematology and Cellular Therapy, Pembroke Pines, FL

See more of: Education Program