Immunomodulatory effect of dasatinib plus blinatumomab versus ponatinib plus blinatumomab in newly diagnosed Ph+ acute lymphoblastic leukemia.

In Ph+ acute lymphoblastic leukemia, frontline dasatinib plus blinatumomab (dasa+blina) is associated with long-term survival rates of 75-80%. The phase III GIMEMA ALL2820 trial has explored ponatinib with blinatumomab (pona+blina). In the present study, the immune modulation induced by dasa+blina and pona+blina was investigated. Immune cells were analyzed at the end of induction (T0) and after 2, 4 and 5 blinatumomab cycles (T2, T4, T5). Among 153 patients (43 dasa+blina, 110 pona+blina), the dasa+blina combination induced a significantly greater lymphocyte increase at T4 and T5 compared to pona+blina. The Treg counts decreased only in the dasa+blina treated patients. NK and NK-T cells increased significantly in the dasa+blina group, at all timepoints. Complete molecular responders (CMR) after dasatinib induction had significantly higher lymphocytes, T and NK cells compared to non-CMR patients. Bone marrow analyses showed higher activation (CD25, CD69) and lower exhaustion (PD1, TIM3) markers on NK and NK-T cells in dasa+blina treated patients. Dasa+blina patients exhibited a significantly enhanced NK cell capacity compared to ponatinib treated patients. Patients remaining on dasatinib maintained elevated NK cells with a more mature phenotype, suggesting a durable effect. These results highlight the greater dasa+blina immune activation, supporting a potential synergistic effect of the drug combination.