Chemotherapy-Free Dasatinib-Blinatumomab Strategy Yields 60% Molecular Response in Ph+ ALL
The D-ALBA phase 2 trial treated 63 adults with newly diagnosed Ph-positive ALL using dasatinib induction followed by blinatumomab consolidation, without conventional chemotherapy. Molecular response by RT-qPCR increased from 29% after induction to 60% after blinatumomab, with 95% overall survival at 18 months. Notably, ABL1 resistance mutations detected by molecular monitoring during induction were cleared by blinatumomab, demonstrating MRD tracking as a tool for real-time treatment adaptation.
The original study
Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults.
- Authors
- Foà R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, et al.
- Journal
- The New England journal of medicine
- Type
- Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't
- PMID
- 33085860
Original 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: 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.).