Blinatumomab for infants with KMT2A-rearranged ALL

Infants with acute lymphoblastic leukemia (ALL) harbouring a KMT2A rearrangement represent a high-risk patient population. Although blinatumomab has demonstrated substantial efficacy in adult ALL patients, its role in frontline treatment for infants has remained less well established. Long-term follow-up data of a phase II, single arm interventional study presented by Dr Miguel Vieira (Martins Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands) at EHA 2026 provide evidence supporting the incorporation of blinatumomab into the frontline treatment for these patients.

The study evaluated the addition of a single cycle of blinatumomab to the Interfant-06 chemotherapy protocol. The objective was to determine whether early incorporation of blinatumomab could improve outcomes while potentially reducing disease- and treatment-related toxicity. The analysis also examined the impact of blinatumomab on immunoglobulin G (IgG) levels, an important consideration given the B-cell-depleting effect of this agent.

Previously published results demonstrated marked improvements in clinical outcomes, with disease-free survival increasing from approximately 45% to 83% and overall survival from 60% to 93%. The current analysis focused on longer-term outcomes and showed that, after four years of follow-up, no additional disease-related events had occurred, indicating that the benefit observed with blinatumomab was maintained over time.

Assessment of IgG recovery showed that levels generally declined following blinatumomab treatment, reaching their lowest point shortly after therapy cessation. This pattern differs from observations in adults, where the lowest IgG levels are typically observed later during the treatment course and recovery being a more prolonged process. In the infant cohort, IgG concentrations increased gradually, with nearly all patients having normalized levels by the end of treatment. These findings suggest a distinct pattern of immune recovery in infants receiving blinatumomab and highlight the importance of systematic monitoring of IgG levels following treatment to better characterize their evolution and recovery.