Dasatinib/Prednisone Induction Followed by Blinatumomab/Dasatinib in Ph+ Acute Lymphoblastic Leukemia.

Novel treatment strategies are needed for the treatment of Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) in older patients. This trial evaluated the feasibility and outcomes with the anti-CD19 bispecific T-cell engaging antibody, blinatumomab, in combination with dasatinib and steroids. Patients 65 years of age or older with Ph+ or Ph-like ALL (with dasatinib sensitive fusions/ mutations) were eligible and could be newly diagnosed or relapsed/ refractory. Induction therapy consisted of dasatinib/ prednisone. Patients not achieving response by Day 56 proceeded to blinatumomab re-induction therapy. Patients achieving response with induction or re-induction therapy proceeded to blinatumomab/ dasatinib post-remission therapy for 3 cycles followed by dasatinib/ prednisone maintenance. All patients received central nervous system prophylaxis with intrathecal methotrexate for a total of 8 doses. Response was assessed at Days 28, 56, 84, and at additional time points based on response parameters. Measurable residual disease (MRD) was assessed centrally by 8 color flow cytometry at Day 28. Twenty-four eligible patients with newly diagnosed Ph+ ALL were enrolled with a median age of 73 years (range 65-87). This combination was safe and feasible. With a median of 2.7 years of follow up, 3-year overall survival and disease-free survival were 87% (95% CI 64%-96%) and 77% (95% CI 54%-90%), respectively. Although longer follow up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial is registered at www.clinicaltrials.gov as NCT02143414.