Dasatinib–Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults
Robin Foà, Renato Bassan, Antonella Vitale, Loredana Elia, Alfonso Piciocchi, Maria Cristina Puzzolo, Martina Canichella, Piera Viero, Felicetto Ferrara, Monia Lunghi, Francesco Fabbiano, Massimiliano Bonifacio, Nicola Fracchiolla, Paolo Di Bartolomeo, Alessandra Mancino, Maria-Stefania De Propris, Marco Vignetti, Anna Guarini, Alessandro Rambaldi, Sabina Chiaretti
Abstract
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: 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.).