ENHANCED Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia immune activation was observed with frontline dasatinib plus blinatumomab compared with ponatinib plus blinatumomab, according to detailed immune analyses from a large clinical cohort. The findings indicate broader and more durable immune modulation with dasatinib based treatment and support a synergistic interaction between targeted therapy and immunotherapy.
Study Design and Immune Assessment
The investigation examined immune changes in patients with Philadelphia chromosome positive acute lymphoblastic leukaemia treated with either dasatinib plus blinatumomab or ponatinib plus blinatumomab. Immune cell populations were evaluated at the end of induction and after two, four and five cycles of blinatumomab. Data from 153 patients were analysed, including 43 treated with dasatinib plus blinatumomab and 110 treated with ponatinib plus blinatumomab.
Lymphocyte dynamics differed significantly between regimens. Patients receiving dasatinib plus blinatumomab showed a greater increase in lymphocyte counts at later timepoints, particularly after four and five cycles. Regulatory T cell counts decreased only in those receiving dasatinib based therapy, suggesting a shift towards a more active immune profile.
Leukaemia Immune Activation
Ph+ acute lymphoblastic leukaemia immune activation was especially evident in the natural killer and natural killer T cell compartments. These cell populations increased significantly at all assessed timepoints in patients treated with dasatinib plus blinatumomab, whereas more limited changes were seen with ponatinib based therapy.
Patients achieving complete molecular response after dasatinib induction demonstrated higher lymphocyte, T cell and natural killer cell levels compared with those without complete molecular response. Bone marrow analyses further showed increased expression of activation markers (CD25, CD69) and reduced expression of exhaustion markers (PD1, TIM3) on natural killer and natural killer T cells in the dasatinib group.
Durable Immune Effects and Clinical Implications
Functional assessments revealed a significantly enhanced natural killer cell capacity in patients treated with dasatinib plus blinatumomab compared with ponatinib treated patients. Importantly, individuals who remained on dasatinib maintained elevated natural killer cell levels with a more mature phenotype, indicating a durable immunological effect.
Together, these data highlight stronger and sustained Ph+ acute lymphoblastic leukaemia immune activation with dasatinib plus blinatumomab and suggest that immune modulation may contribute meaningfully to the favourable long-term outcomes previously reported with this regimen.
Reference
Zeng Y et al. Sarcopenia, myosteatosis and systemic immunoinflammatory index in the prediction of survival in patients undergoing immunotherapy for esophageal cancer. Scientific Reports. 2026; https://doi.org/10.1038/s41598-025-34513-2.
