title: Evolution to plasmablastic lymphoma evades CD19-directed chimeric antigen receptor T cells.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Evans
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Rothberg
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: W Richard
authors.initials: WR
authors.lastname: Burack
authors.affiliation: Department of Medicine and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Scott F
authors.initials: SF
authors.lastname: Huntington
authors.affiliation: Department of Medicine and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Porter
authors.affiliation: Department of Medicine and James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.affiliation: Department of Medicine and James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Liesveld
keywords: chimeric antigen receptor T cells; chronic lymphocytic leukaemia; leukaemia; lymphoma; plasmablastic