Breast Cancer

Dasatinib–Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults

In the following article, published October 22, 2020 in the New England Journal of Medicine, investigators sought to assess the feasibility of treating patients with Philadelphia chromosome positive acute lymphoblastic leukemia, with a combination of dasatinib and blinatumomab. In this phase 2 clinical trial, adults with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia, were treated in first-line setting with dasatinib plus glucocorticoids, followed by 2 cycles of blinatumomab. The primary endpoint was sustained molecular response in the bone marrow. 63 patients were involved. The mean age was 54, range 24-82. A complete remission was observed in the 98%. When patients reached the end of dasatinib induction, day 85, 29% of patients had a molecular response with this percentage increasing to 60% after 2 cycles of blinatumomab. The percentage of patients who had a molecular response increased even further after additional blinatumomab. The overall survival was 90% after a median follow-up of 18 months. The disease-free survival was 88%. For patients that harbored a IKZF1 deletion, plus additional genetic mutations (CDKN2A or CDKN2B, PAX5, or both [i.e., IKZF1plus] ), the disease-free survival was lower. ABL1 mutations were detected in 6 patients who showed an increase in minimal residual disease during induction therapy, Infusion with blinatumomab, cleared these. There were 6 relapses. Grade 3 or 4 adverse events were reported 21 times. 24 patients underlined allogeneic stem cell transplantation, with 1 transplant related death. The authors concluded that a chemotherapy-free induction and consolidation in the first-line setting for Philadelphia chromosome positive acute lymphoblastic leukemia in adults, with dasatinib, corticosteroids, and blinatumomab showed a high incidence of molecular response and survival with few toxic adverse events.