Pre-treatment intrinsic T cell features and immune milieu characteristics shape response to Blinatumomab in patients with B-cell Precursor Acute Lymphoblastic Leukemia

Longitudinally, NR exhibited expansion of TIM3⁺CD8⁺ T cells (time×response β=1.91, p=0.025) and impaired T cell function. The Blina-induced peak of TIM3⁺CD8⁺ T cells correlated positively with baseline CXCR4 (r=0.88, p=0.03) and inversely with ZNF683 (r=–0.89, p=0.03) expression in CD8+TEMs. Non-responders exhibited higher circulating levels of immunosuppressive proteins, including CSF-1, ICOSLG, and Galectin-9, throughout the first treatment cycle.

To our knowledge, this is the largest study to determine factors of treatment resistance to blinatumomab. A pre-existing immunosuppressive milieu and subsequent treatment-induced T-cell exhaustion are associated with treatment failure and might serve as biomarkers for risk stratification as well as potential targets to enhance Blina efficacy in BCP-ALL.