Long-Term Results of the Dasatinib-Blinatumomab Protocol for Adult Philadelphia-Positive ALL

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report the long-term results of the frontline trial with dasatinib and blinatumomab in induction/consolidation (GIMEMA LAL2116, D-ALBA) for adult Philadelphia-positive ALL (Ph+ ALL), which enrolled 63 patients of all ages. At a median follow-up of 53 months, disease-free survival, overall survival, and event-free survival are 75.8%, 80.7%, and 74.6%, respectively. No events have occurred among early molecular responders. A significantly worse outcome was recorded for IKZF1^plus patients. Twenty-nine patients-93.1% being in molecular response (ie, complete molecular response or positive nonquantifiable) after dasatinib/blinatumomab-never received chemotherapy/transplant and continued with a tyrosine kinase inhibitor only; 28 patients remain in long-term complete hematologic response (CHR). An allogeneic transplant was carried out in first CHR mainly in patients with persistent minimal residual disease; 83.3% of patients are in continuous CHR. The transplant-related mortality was 12.5% for patients transplanted in first CHR and 13.7% overall. Nine relapses and six deaths have occurred. ABL1 mutations were found in seven cases. The final analysis of the D-ALBA study shows that a chemotherapy-free induction/consolidation regimen on the basis of a targeted strategy (dasatinib) and immunotherapy (blinatumomab) is effective in inducing durable long-term hematologic and molecular responses in adult Ph+ ALL, paving the way for a new era in the management of these patients.

Trial registration: ClinicalTrials.gov NCT02744768.

FIG 1.

(A) DFS, (B) OS, and (C) EFS calculated from the EOI (d +85) and diagnosis/treatment initiation. The shadings of each curve show the 95% CI at a median follow-up of 53 months. DFS, disease-free survival; EFS, event-free survival; EOI, end of induction; OS, overall survival.

FIG 2.

(A and B) DFS and (C and D) OS according to molecular response. DFS was calculated from (A) EOI (d +85) and after the (B) second cycle of blinatumomab (primary end point); OS was calculated from diagnosis/treatment initiation stratifying patients according to molecular response at the (C) EOI (d +85) and (D) after the second cycle of blinatumomab. Blue line: molecular responders; red line: nonmolecular responders. The shadings of each curve show the 95% CI. CMR, complete molecular response; DFS, disease-free survival; EOI, end of induction; OS, overall survival; PNQ, positive nonquantifiable.