Ibrutinib Improves CAR T-cell Function, Efficacy in Leukemia

Improved T-cell function may aid the efficacy of ibrutinib in patients with chronic lymphocytic leukemia (CLL), according to a study published in the Annals of Oncology.¹

Although anti-CD chimeric antigen receptor (CAR) T-cell therapy is promising, it requires robust T-cell expansion and engraftment.

Response to CAR T-cells can be lessened by a T-cell defect in patients with CLL caused by treatment or disease. Ex vivo expansion can also be lessened.

Investigators sought to evaluate the effect of ibrutinib on the T-cell compartment in CLL as it related to CAR T-cell generation. The phenotype and function of T-cells were examined in a cohort of patients with CLL during their treatment course with ibrutinib.

Results showed that 5 or more cycles of ibrutinib increased the expansion of CD19-directed CAR T-cells (CTLO19) and decreased immunosuppressive molecules PD1 on T-cells and CD200 on B-CLL cells.

Three patients with CLL who had been treated with ibrutinib for at least one year had improved ex vivo and in vivo CTLO19 expansion, which was linked to a positive clinical response.

Ibrutinib exposure improved CAR T-cell engraftment, tumor clearance, and survival in human xenograft models of resistant acute lymphocytic leukemia and CLL.

“Our collective findings indicate that ibrutinib enhances CAR T-cell function and suggest that clinical trials with combination therapy are warranted. Finally, our studies demonstrate that improved T-cell function may also contribute to the efficacy of ibrutinib in CLL,” the study authors concluded.

Reference

1. Fraietta JA, Bechwith KA, Patel PR, et al. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia [published ahead of time on January 26, 2016]. Blood. doi: 10.1182/blood-2015-11-679134.