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- Title
Evolution to plasmablastic lymphoma evades CD19-directed chimeric antigen receptor T cells.
- Authors
Evans, Andrew G.; Rothberg, Paul G.; Burack, W. Richard; Huntington, Scott F.; Porter, David L.; Friedberg, Jonathan W.; Liesveld, Jane L.
- 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.
- Subjects
CHRONIC lymphocytic leukemia; LYMPHOMAS; T cells; ANTIGEN receptors; IMMUNOTHERAPY
- Publication
British Journal of Haematology, 2015, Vol 171, Issue 2, p205
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.13562