Upfront treatment with the first and second-generation tyrosine kinase inhibitors in Ph-positive acute lymphoblastic leukemia

Abstract

The treatment of Ph-positive acute lymphoblastic leukemia (Ph+ ALL) has entranced tyrosine kinase inhibitors (TKIs) era. Currently both imatinib and dasatinib are registered as the front-line treatment for Ph+ ALL, and the other 2^nd-generation TKIs are suggested as an alternative for those who failed the first-line treatment. However, it remains unclear who could benefit from the 2^nd-generation TKIs as the first-line treatment for Ph+ ALL. In this study we compared the efficacy and safety of the 1^st and 2^nd-generation TKIs in the front-line treatment of Ph+ ALL and found a trend toward better disease-free survival (DFS) in the 2^nd-generation TKIs group, though no significant difference in early response and long-term survival between the two groups. Furthermore, subgroup analysis showed that if allogeneic hematopoietic stem cell transplantation (allo-HSCT) was incorporated as consolidation, the 2^nd-generation TKIs benefited patients with better DFS and overall survival (OS). The two generation TKIs were well tolerated. Higher incidence of acquiring T315I mutation was observed in the patients relapsed on the 2^nd-generation TKIs. These findings suggested front-line treatment of Ph+ ALL with the 2^nd-generation TKIs might benefit patients with better survival when allo-HSCT was incorporated as consolidation therapy; meanwhile, the higher incidence of T315I mutation in patients relapsed on the 2^nd-generation TKIs deserved further attention.