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Evolution to plasmablastic lymphoma evades CD19‐directed chimeric antigen receptor T cells
Author(s) -
Evans Andrew G.,
Rothberg Paul G.,
Burack W. Richard,
Huntington Scott F.,
Porter David L.,
Friedberg Jonathan W.,
Liesveld Jane L.
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13562
Subject(s) - chimeric antigen receptor , cd19 , lymphoma , antigen , immunotherapy , immunology , cancer research , plasmablastic lymphoma , biology , medicine , immune system
Summary 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.