Modern Management Options for Ph+ ALL

SIMPLE SUMMARY: The use of tyrosine kinase inhibitors has represented a major step forward in the therapy of Philadelphia chromosome positive acute lymphoblastic leukemia. Recent improvements in the therapy are focused on early use of third generation tyrosine kinase inhibitors, their combination with immunotherapy, the refined indication of allogeneic hematopoietic stem cell transplantation, the optimal use and duration of maintenance therapy, and the management of patients with molecular or hematological relapse with combination of targeted therapies and immunotherapy, including cellular therapies. Improvements in the assessment of measurable residual disease and in the detection of mutations in the ABL1 domain are contributing to the better selection of the therapy for newly diagnosed as well as for relapsed or refractory patients. ABSTRACT: Impressive advances have been achieved in the management of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) since the initial concurrent use of imatinib and standard chemotherapy. The attenuation of chemotherapy has proven to be equally effective and less toxic, the use of third generation TKI upfront has improved the frequency of complete molecular response and the survival rate, and the combination of tyrosine kinase inhibitors with immunotherapy has further increased the rate of molecular response to 70–80% after consolidation, which has been translated into a survival rate of 75–90% in recent trials. As a result of these improvements, the role of allogeneic hematopoietic stem cell transplantation is being redefined. The methodology of measurable residual disease assessment and the detection of ABL1 mutations are also improving and will contribute to a more precise selection of the treatment for newly diagnosed and relapsed or refractory (R/R) patients. Finally, new compounds combined with immunotherapeutic approaches, including cellular therapy, are being used as rescue therapy and will hopefully be included in first line therapy in the near future. This article will review and update the modern management of patients with Ph+ ALL.