Blinatumomab (CD19xCD3 BiTE) Replaces 2 Chemo Blocks and Improves 4-year EFS in Pediatric High-Risk B-ALL

Blinatumomab (Blincyto), a CD19xCD3 bispecific T-cell engager that redirects T cells to kill CD19+ B-lineage blasts, was tested in the randomized Phase 3 AIEOP-BFM ALL 2017 study (EudraCT 2016-001935-12; NCT03643276) as a chemotherapy-replacement strategy after consolidation for newly diagnosed high-risk B-cell ALL. Children were randomized 1:1 to receive two cycles of blinatumomab vs two cycles of intensive multi-agent chemotherapy (n=709 randomized; 358 vs 351); at a planned interim analysis (median follow-up 2.9 years), estimated 4-year event-free survival was 83.0% vs 70.3% (HR 0.51, 95% CI 0.35–0.73; P=0.0002), a clinically meaningful delta vs the trial’s own chemo control (i.e., not just “non-inferior” to SOC, but better). Treatment-related infection rates strongly favored blinatumomab (23.9% vs 69.4%; P<0.001) and life-threatening AEs were lower (0.5% vs 4.7%), but immune/neuro-tox signals were higher with blinatumomab (neurotoxicity 12.0% vs 3.2%; P<0.001) with low grade ≥2 cytokine release syndrome (1.1%).