BACKGROUND: Outcomes in patients with Philadelphia chromosome (Ph)-positive 
acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase 
inhibitors. Molecular remission is a primary goal of treatment.
METHODS: We conducted a phase 2 single-group trial of first-line therapy in 
adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib 
plus glucocorticoids were administered, followed by two cycles of blinatumomab. 
The primary end point was a sustained molecular response in the bone marrow 
after this treatment.
RESULTS: Of the 63 patients (median age, 54 years; range, 24 to 82) who were 
enrolled, a complete remission was observed in 98%. At the end of dasatinib 
induction therapy (day 85), 29% of the patients had a molecular response, and 
this percentage increased to 60% after two cycles of blinatumomab; the 
percentage of patients with a molecular response increased further after 
additional blinatumomab cycles. At a median follow-up of 18 months, overall 
survival was 95% and disease-free survival was 88%; disease-free survival was 
lower among patients who had an IKZF1 deletion plus additional genetic 
aberrations (CDKN2A or CDKN2B, PAX5, or both [i.e., IKZF1 plus]). ABL1 mutations 
were detected in 6 patients who had increased minimal residual disease during 
induction therapy, and all these mutations were cleared by blinatumomab. Six 
relapses occurred. Overall, 21 adverse events of grade 3 or higher were 
recorded. A total of 24 patients received a stem-cell allograft, and 1 death was 
related to transplantation (4%).
CONCLUSIONS: A chemotherapy-free induction and consolidation first-line 
treatment with dasatinib and blinatumomab that was based on a targeted and 
immunotherapeutic strategy was associated with high incidences of molecular 
response and survival and few toxic effects of grade 3 or higher in adults with 
Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and 
others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov 
number, NCT02744768.).