New Investigator Research Grant Program

2022-2023

David Kurtz, MD, PhD

Assistant Professor of Medicine (Oncology)
Stanford University School of Medicine

Research project

Determinants of Resistance to BCMA-Targeted Chimeric Antigen Receptor T-Cells in Multiple Myeloma from Cell-Free DNA

Summary

Multiple myeloma (MM) is the second most common blood cancer. While new treatments have emerged for MM in the last decade, most patients will have their disease come back after treatment. One of the most promising new treatments for MM is a called a “chimeric antigen receptor T-cell”, or CAR T-cell for short. These CAR T-cells harness the power of the immune system to treat cancer, often leading to significant responses in patients with MM. However, despite how well these CAR T-cells initially work, the MM disease will almost always return and become resistant to treatment. The reasons that MM stops responding to CAR T-cell treatment is not currently known. In this project, we will discover the reasons that MM becomes resistant to treatment. By using ‘liquid biopsies’ to detect tumor DNA molecules directly from a simple blood draw, this project will reveal the specific mutations in DNA that lead to resistance to CAR T-cells targeting BCMA, a molecule found on MM cells. This project will lead a better understanding of which patients respond to CAR T-cells, and which do not. This will lead to next-generation approaches for MM therapies.

Impact

The results of this study and award will be impactful to the field in many ways. Specifically, the growing role of cell-free DNA in tracking cancers and understanding disease biology is becoming more established, but little data exists for many hematology cancers.

Through my research, we have previously shown that ctDNA is a useful biomarker in lymphomas, and now through this project, this has also been established for myeloma.

This likely indicates that ctDNA is a useful biomarker across nearly all blood cancers, which will enable further studies which can use this biomarker for personalized treatment approaches.

Publication

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Leukemia Research Foundation grant
$100K awarded in 2022

Disease focus
Multiple myeloma

Research focus
Treatment (immuntherapy)