Which tyrosine kinase inhibitor should we use to treat Philadelphia chromosome-positive acute lymphoblastic leukemia?

The incorporation of tyrosine kinase inhibitors (TKIs) into chemotherapy regimens has significantly improved the long-term survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Successive generations of TKIs with increased potency against BCR-ABL and broader spectrum of activity against ABL kinase domain mutations have led to incremental improvements in the outcomes of patients with this disease. In particular, ponatinib, a potent pan-BCR-ABL TKI capable of overcoming the T315I mutation, holds significant promise in the treatment of Ph+ ALL, although the potential cardiovascular toxicity of this agent remains a concern. With the development of more potent TKIs that are capable of inducing deep and sustained remissions, future studies re-evaluating the need for intensive chemotherapy as well as the role for stem cell transplantation in first remission for patients with Ph+ ALL are warranted.