达沙替尼联合贝林妥欧单抗对比帕纳替尼联合贝林妥欧单抗在新诊断 Ph+ 急性淋巴细胞白血病中的免疫调节作用

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.