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.
CITATION STYLE
Evans, A. G., Rothberg, P. G., Burack, W. R., Huntington, S. F., Porter, D. L., Friedberg, J. W., & Liesveld, J. L. (2015). Evolution to plasmablastic lymphoma evades CD19-directed chimeric antigen receptor T cells. British Journal of Haematology, 171(2), 205–209. https://doi.org/10.1111/bjh.13562
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