GIMEMA ALL2820 phase III trial: Ponatinib + blinatumomab vs imatinib + chemotherapy in Ph+ ALL

Results from the randomized, phase III GIMEMA ALL2820 trial (NCT04722848) evaluating ponatinib + blinatumomab vs imatinib + chemotherapy in adults with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were published in the New England Journal of Medicine by Chiaretti et al. The primary endpoint was event-free survival (EFS).

Key data: At a median follow-up of 23.7 months, the estimated 24-month EFS was 86% (95% confidence interval [CI], 80–92) with ponatinib + blinatumomab (n = 158) vs 67% (95% CI, 56–79) with imatinib + chemotherapy (n = 78; p <0.001); estimated 24-month overall survival (OS) was 90% vs 85%, respectively, and the cumulative incidence of relapse (CIR) was 5% vs 13%, respectively. At the end of induction (Day 70), molecular response rates were 47% with ponatinib + blinatumomab vs 44% with imatinib + chemotherapy; following consolidation (Day 133), molecular response rates were 71% vs 49%, respectively. Grade ≥3 severe adverse events occurred in 34% vs 47% of patients, respectively.

Key learning: In GIMEMA ALL2820, ponatinib + blinatumomab demonstrated superior EFS vs imatinib + chemotherapy in adults with Ph+ ALL, supporting the potential of this chemotherapy-free approach as a first-line treatment option in this population; however, longer follow-up is needed.