1. Treatment with dasatinib and blinatumomab was associated with high incidence of molecular response in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL).
2. Treatment with dasatinib and blinatumomab for patients with Ph-positive ALL was associated with a high incidence of survival.
Evidence Rating Level: 2 (Good)
Study Rundown: Prognosis for Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) in adults has improved since the introduction of ABL-specific tyrosine kinase inhibitors. The use of these therapeutics with a chemotherapy-free induction strategy requires a prephase treatment with glucocorticoids followed by an induction phase with a tyrosine kinase inhibitor plus glucocorticoids. This treatment strategy has resulted in greater percentage of patients having a complete hematologic response. As such, this trial evaluated a first-line tyrosine kinase inhibitor therapy in adults with newly diagnosed Ph-positive ALL. The therapy included induction with dasatinib, a second generation ABL tyrosine kinase inhibitor, followed by consolidation with blinatumomab, a bispecific anti-CD3 and anti-CD19 monoclonal antibody. The study results showed treatment with dasatinib and blinatumomab was associated with high incidence of molecular response and survival. This prospective cohort study was limited by the small patient population and the rapid acquisition of deleterious mutations amongst the cancer cells. Nonetheless, this study’s results are significant, and its findings highlight a chemotherapy-free induction strategy in the treatment of Ph-positive ALL.
In-Depth [prospective cohort]: This prospective cohort study enrolled 63 patients as a part of the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) cooperative trial group initiative. Patients included in the study were ≥18 years of age and newly diagnosed with Ph-positive ALL. Patients without molecular assay detection of the BCR-ABL1 fusion product were excluded from the study. Prephase glucocorticoid treatment lasted for seven days prior to patients receiving dasatinib. Glucocorticoid treatment continued for another 24 days prior to discontinuation on day 31. Dasatinib was administered at 140 milligrams once daily as induction therapy. Upon completion of the induction phase, blinatumomab was given at a dose of 28 micrograms per day for a minimum of two cycles. The primary end point was a molecular response defined by the BCR-ABL1 to ABL1 ratio at the end of the second blinatumomab cycle. The median age of the patients was 54 years (range, 24 to 82). At the completion of the induction period, 98% of the patients (62 of 63 patients) had a complete hematologic response defined as 5% bone marrow blasts or less, the absence of blasts in peripheral blood, no extramedullary involvement, and complete recovery of peripheral blood count. Additionally, 29% of the patients (17 out of 59 patients) had a molecular response at the end of the induction period, while 60% of patients (33 of 55 patients) had a molecular response at the time of the primary end point. The median follow-up was 18 months (range, 1 to 25). Overall survival was 95% (95% confidence interval [CI], 90 to 100) along with disease-free survival being 88% (95% CI, 80 to 97). Specifically, disease-free survival in patients with a molecular response at end of induction period was 100% compared to 85% of patients with a non-molecular response. Finally, longitudinal data was evaluated in 17 patients, which showed a decrease in the Tregs percentage and the CD4+/CD8+ ratio in patients receiving the third cycle of blinatumomab. The trends were maintained after the fourth and fifth cycles. Taken together, dasatinib and blinatumomab treatment in patients with Ph-positive ALL was associated with high incidence of molecular response and disease-free survival.
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