• Vinodh Pillai, Kavitha Muralidharan, Wenzhao Meng, Asen Bagashev, Derek A Oldridge, Jaclyn Rosenthal, John Van Arnam, Jos J Melenhorst, Diwakar Mohan, Amanda M DiNofia, Minjie Luo, Sindhu Cherian, Jonathan R Fromm, Gerald Wertheim, Andrei Thomas-Tikhonenko, Michele Paessler, Carl H June, Eline T Luning Prak, Vijay G Bhoj, Stephan A Grupp, Shannon L Maude, and Susan R Rheingold.
• Department of Pathology and Laboratory Medicine and.
• Blood Adv. 2019 Nov 26; 3 (22): 3539-3549.

AbstractTisagenlecleucel, a chimeric antigen receptor (CAR) T-cell product targeting CD19 is approved for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, the impact of pretreatment variables, such as CD19 expression level, on leukemic blasts, the presence of CD19- subpopulations, and especially prior CD19-targeted therapy, on the response to CAR T-cell therapy has not been determined. We analyzed 166 patients treated with CAR T-cell therapy at our institution. Eleven patients did not achieve a minimal residual disease (MRD)- deep remission, whereas 67 patients had a recurrence after achieving a MRD- deep remission: 28 patients with CD19+ leukemia and 39 patients with CD19- leukemia. Return of CD19+ leukemia was associated with loss of CAR T-cell function, whereas CD19- leukemia was associated with continued CAR T-cell function. There were no significant differences in efficacy of CAR T cells in CD19-dim B-ALL, compared with CD19-normal or -bright B-ALL. Consistent with this, CAR T cells recognized and lysed cells with very low levels of CD19 expression in vitro. The presence of dim CD19 or rare CD19- events by flow cytometry did not predict nonresponse or recurrence after CAR T-cell therapy. However, prior therapy with the CD19-directed, bispecific T-cell engager blinatumomab was associated with a significantly higher rate of failure to achieve MRD- remission or subsequent loss of remission with antigen escape. Finally, immunophenotypic heterogeneity and lineage plasticity were independent of underlying clonotype and cytogenetic abnormalities.© 2019 by The American Society of Hematology.

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