Evidence-Based Minireview: What is the optimal tyrosine kinase inhibitor for adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia?

Abstract

The incorporation of BCR::ABL1 tyrosine kinase inhibitors (TKIs) to intensive chemotherapy significantly improved the outcomes of patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). This was first shown with the addition of the first-generation TKI imatinib, which allowed more patients to be bridged to an allogeneic stem cell transplant (SCT) and led to superior long-term outcomes compared with chemotherapy alone. The use of second-generation TKIs (eg, dasatinib and nilotinib) has led to further improvement in outcomes of patients with Ph- positive ALL, with a long-term survival of 40% to 60% in several studies. Ponatinib is a third-generation, more potent TKI that results in high rates of molecular response and promising long-term survival even when allogeneic SCT is not routinely performed. While randomized data to support the TKI selection in Ph-positive ALL are lacking, data from single-arm studies suggest deeper molecular responses and superior survival outcomes with each successive generation of TKI. More recently, chemotherapy-free regimens with blinatumomab and TKIs have shown excellent results in the frontline setting and may represent an emerging paradigm shift in the treatment of Ph-positive ALL.