1. Evolution to plasmablastic lymphoma evades CD19-directed chimeric antigen receptor T cells.
- Author
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Evans, Andrew G., Rothberg, Paul G., Burack, W. Richard, Huntington, Scott F., Porter, David L., Friedberg, Jonathan W., and Liesveld, Jane L.
- Subjects
CHRONIC lymphocytic leukemia ,LYMPHOMAS ,T cells ,ANTIGEN receptors ,IMMUNOTHERAPY - Abstract
A patient with relapsed and refractory chronic lymphocytic leukaemia with Richter transformation was treated with chimeric antigen receptor ( CAR)-modified T cells targeted for CD19 but later relapsed with a clonally related plasmablastic lymphoma. The loss of most routine markers of pre-plasma cell or B lymphoid differentiation (including CD19) highlights the ability of such mature lymphomas to evade lineage-specific targeted immunotherapy by differentiating along pathways comparable to their normal cellular counterparts. Molecular genetic evaluation demonstrated multiple independent lines of CD19-negative disease that eventually evolved in this single patient. Such plasticity represents potential challenges for antigen-directed CAR-T cell therapy, while serving as a testament to the selective pressure exerted by these engineered T cells over time. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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