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Plasma Cell Dyscrasias: Resistance to Immunotherapy: Mechanisms and Monitoring

PhD Trainee
Sponsor: Scientific Committee on Plasma Cell Neoplasia
Program: Scientific Program
Hematology Disease Topics & Pathways:
Research, Biological therapies, Antibody Therapy, Clinical Practice (Health Services and Quality), Non-Biological therapies, Bispecific Antibody Therapy, Translational Research, genomics, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Plasma Cell Disorders, Diversity, Equity, and Inclusion (DEI) , Diseases, immune mechanism, Therapies, Lymphoid Malignancies, Biological Processes, emerging technologies, Technology and Procedures, Study Population, profiling, Human
Monday, December 12, 2022: 10:30 AM-11:45 AM
New Orleans Theater AB (Ernest N. Morial Convention Center)

Description:
In the last couple of decades we have witnessed tremendous progress in the therapeutics of multiple myeloma. The advent of proteasome inhibitors, immunomodulatory drugs, CD38 directed monoclonal antibodies and more recently B-Cell Maturation Antigen (BCMA) directed therapies have altered the treatment landscape for the disease. However, the malignant cells in this disease do nearly always ultimately develop resistance to the therapeutic modalities and the disease progresses. Understanding mechanisms of resistance to these therapies is therefore vital to improving patient outcomes. 

 

Dr. Flavia Pichiorri will focus on mechanisms of Daratumumab and BCMA therapy resistance which will include an overview of the literature in the field and published and unpublished data produced in her laboratory. 

 

Dr. Sarah Gooding will discuss the challenges of the development of resistance to immunomodulatory drugs (IMiD®) in the long-term management of patients with myeloma.  She will discuss the mechanisms by which resistance may arise; this may be due to the selection of drug resistant subclones during therapy exposure, or changes in the bone marrow and immune microenvironment. The Cereblon drug binding protein may be lost due to a range of mechanisms. Dr. Gooding will discuss whether we may be able to move towards better targeting of IMiD drugs by implementing resistance marker tracking into the clinic. 

 

Dr. Jens Lohr will discuss conceptual advantages of cell-free DNA over disease markers that are currently used in clinical routine care, the benefits and limitations of adding cell-free DNA interrogation to the currently available parameters of response, its value for disease assessment and as a tool to refine clinical decision-making. Liquid biopsy approaches with cell-free DNA interrogation are powerful tools to obtain information about multiple myeloma without the need for invasive bone marrow biopsy.

Chair:
Ravi Vij, MD, MBBS, Washington University in St. Louis
Disclosures:
Vij: Legend: Honoraria; BMS: Honoraria, Research Funding; Pfizer: Honoraria; GSK: Honoraria; Sanofi: Honoraria, Research Funding; Adaptive: Honoraria; Harpoon: Consultancy; Takeda: Honoraria, Research Funding; Oncopeptides: Honoraria; Biegene: Honoraria; Janssen: Honoraria; CareDx: Honoraria.
In the last couple of decades we have witnessed tremendous progress in the therapeutics of multiple myeloma. The advent of proteasome inhibitors, immunomodulatory drugs, CD38 directed monoclonal antibodies and more recently B-Cell Maturation Antigen (BCMA) directed therapies have altered the treatment landscape for the disease. However, the malignant cells in this disease do nearly always ultimately develop resistance to the therapeutic modalities and the disease progresses. Understanding mechanisms of resistance to these therapies is therefore vital to improving patient outcomes. 

 

Dr. Flavia Pichiorri will focus on mechanisms of Daratumumab and BCMA therapy resistance which will include an overview of the literature in the field and published and unpublished data produced in her laboratory. 

 

Dr. Sarah Gooding will discuss the challenges of the development of resistance to immunomodulatory drugs (IMiD®) in the long-term management of patients with myeloma.  She will discuss the mechanisms by which resistance may arise; this may be due to the selection of drug resistant subclones during therapy exposure, or changes in the bone marrow and immune microenvironment. The Cereblon drug binding protein may be lost due to a range of mechanisms. Dr. Gooding will discuss whether we may be able to move towards better targeting of IMiD drugs by implementing resistance marker tracking into the clinic. 

 

Dr. Jens Lohr will discuss conceptual advantages of cell-free DNA over disease markers that are currently used in clinical routine care, the benefits and limitations of adding cell-free DNA interrogation to the currently available parameters of response, its value for disease assessment and as a tool to refine clinical decision-making. Liquid biopsy approaches with cell-free DNA interrogation are powerful tools to obtain information about multiple myeloma without the need for invasive bone marrow biopsy.

Flavia Pichiorri, PhD

Department of Hematologic Malignancies Translational Science, Beckman Research Institute, City of Hope, Duarte, CA

Sarah Gooding, MD, PhD

MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom

Jens G. Lohr, MD, PhD

Dana Farber Cancer Institute, Boston, MA

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