Successful anti‐CD19 CAR T‐cell therapy in HIV‐infected patients with refractory high‐grade B‐cell lymphoma

Abstract

Cancer November 1, 2019 Herein, we have reported on 2 patients with AIDS-associated, high-grade, B-cell lymphoma who were treated with commercially available anti-CD19 chimeric antigen receptor (CAR) T cells for chemotherapy-refractory disease. CAR T cells are autologous T cells that are apheresed from a patient and then transfected to express a CAR. The CAR includes an extracellular antigen recognition domain derived from an antibody, a transmembrane domain or hinge, and intracellular costimulation and signaling domains that activate the T cell. These genetically modified T cells then are expanded in the laboratory and reinfused into the patient, in whom they can now specifically recognize and destroy tumor cells bearing the target antigen. Two CAR T cells, both of which target the B-cell antigen CD19, currently are approved by the US Food and Drug Administration for the treatment of patients with refractory, aggressive B-cell lymphomas. The first patient initially presented at age 47 years with dysphagia and was found to have a large tonsillar mass. Computed tomography (CT) scans confirmed a large right tonsillar mass and multiple enlarged lymph nodes bilaterally. A biopsy of the tonsillar mass demonstrated diffuse large B-cell lymphoma (DLBCL) of germinal center B-cell subtype. In situ hybridization demonstrated no staining for Epstein-Barr virus (EBV)–encoded RNA. The karyotype was hyperdiploid and contained clonal aberrations including trisomies 2, 7, and 21, as well as 12p deletion, 9q deletion, and 14q deletion, none of which to our knowledge are diagnostically specific for a subtype of lymphoma. A staging positron emission tomography (PET)–CT scan demonstrated multifocal intense uptake in bilateral parotid glands and tonsils, extensive adenopathy above and below the diaphragm, and the involvement of the spleen and bone marrow. Bone marrow biopsy confirmed involvement by large B-cell lymphoma. The disease was classified as Ann Arbor stage IV and the patient’s International Prognostic Index score was 3.