Positive survival outcomes were observed in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) when treated with dasatinib followed by blinatumomab in in a phase 2 study now published in the New England Journal of Medicine.
For the trial, adults with newly diagnosed Ph-positive ALL were given a seven-day prephase treatment with a glucocorticoid prior to the first administration of dasatinib in a 140 mg dose. Glucocorticoids were continued for 24 more days and halted on day 31. Dasatinib induction therapy continued for 85 days, followed by two cycles of blinatumomab. The study evaluated sustained molecular response in the bone marrow after treatment as the primary end point.
Of the 61 patients who completed the induction phase, 58 received one cycle of blinatumomab, 56 received two cycles, 45 received three cycles, 37 received four cycles, and 29 received five cycles. The median start time between dasatinib induction therapy and the start of blinatumomab treatment was 10 days.
Of the 63 patients enrolled in the trial, 98% achieved complete remission. Following dasatinib induction therapy, 29% of patients had a molecular response. When two cycles of blinatumomab were added, the molecular response rate increased to 60%; it increased further after additional cycles of blinatumomab. A follow-up at a median of 18 months found an overall survival rate of 95% and a disease-free survival rate of 88%. There were 21 adverse events of grade 3 or higher. Twenty-four patients received a stem-cell allograft, and 1 death (4%) was related to transplantation.
"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," conclude the investigators, led by first author Robin Foà, MD, Professor and Head of the Division of Hematology at the Sapienza University of Rome, Italy.
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