Evolution to plasmablastic lymphoma evades CD19-directed chimeric antigen receptor T cells.

Br J Haematol 2015 Oct 18;171(2):205-209. Epub 2015 Jun 18.

Department of Medicine and James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.

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.

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http://dx.doi.org/10.1111/bjh.13562DOI Listing
October 2015
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References

(Supplied by CrossRef)
Chimeric antigen receptor-modified T cells for acute lymphoid leukemia
Grupp et al.
New England Journal of Medicine 2013
Plasmablastic transformation of low-grade B-cell lymphomas: report on 6 cases
Martinez et al.
American Journal of Surgical Pathology 2013
Chimeric antigen receptor T cells for sustained remissions in leukemia
Maude et al.
New England Journal of Medicine 2014

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