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.
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“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.
- 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.