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<p>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.</p><p></p>

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

  • 期刊论文

  • 发表日期：

    2026年1月22日

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  • Michela Ansuinelli,
  • Nadia Peragine,
  • Maria Stefania De Propris,
  • Maria Cristina Puzzolo,
  • Mariangela Di Trani,
  • Loredana Elia,
  • Cristina Skert,
  • Roberto Cairoli,
  • Simona Sica,
  • Alessandro Rambaldi,
  • Alessandra Tucci,
  • Marco Cerrano,
  • Daniele Vallisa,
  • Valeria Cardinali,
  • Antonino Mulè,
  • Sabina Chiaretti,
  • Anna Guarini,
  • Robin Foà

摘要

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.