Multicenter phase 3 trial of frontline ponatinib-blinatumomab or imatinib-chemotherapy for Ph-positive ALL in adult patients

The outcome of Ph-positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the use of tyrosine kinase inhibitors and immunotherapy. The multicenter phase 3 GIMEMA trial in Italy evaluated the combination of ponatinib and blinatumomab (intervention group) versus imatinib plus chemotherapy (control group) as frontline therapy for Ph+ ALL in adult patients. Patients were randomized 2:1 to intervention (n=158) or control (n=78), with crossover to intervention permitted for patients with persistence or reappearance of measurable disease in the control group. The primary endpoint was event-free survival (EFS). At a median follow-up of 23.7 months, the estimated 24-month EFS-rate was 86% in the intervention group and 67% in the control group (p<0.001); survival rate with no measurable residual disease was 68% and 42%, respectively. At the end of induction, a complete hematologic response was seen in 94% of the patients in the intervention group and 79% of those in the control group. After blinatumomab consolidation, a molecular response was observed in 71% and 49% of the patients, respectively. After crossover to the intervention group, 20 of 31 patients (64%) had a molecular response. Overall survival was 90% in the intervention group and 85% in the control group. The cumulative incidence of relapse was 5% and 13%. The authors conclude that a frontline chemotherapy-free targeted and immunotherapeutic approach was superior to the use of imatinib and chemotherapy (quick take video summary).