Sustained Benefit of Blinatumomab in Infants With KMT2A-Rearranged ALL: Long-Term Outcomes, Toxicity, and Pharmacokinetics.

KMT2A-rearranged infant ALL (KMT2A-r ALL) has a poor prognosis. Adding blinatumomab, a bispecific T-cell engager targeting CD19, to standard chemotherapy for infants with KMT2A-r ALL improved short-term outcomes. Here, we present long-term results, toxicity, and pharmacokinetics of blinatumomab from this study. Thirty infants received Interfant-06 protocol chemotherapy with one additional postinduction blinatumomab course. Disease-free survival (DFS) and overall survival (OS) were compared with a historical Interfant-06-selected cohort without blinatumomab. Infection and administration of intravenous immunoglobulin (IVIg) and granulocyte-colony stimulating factor (G-CSF) were documented. Blinatumomab's steady-state concentration (Css) and clearance (CL) were analyzed. The median follow-up was 4.2 years (range, 3.2-6.0). Blinatumomab significantly improved outcomes compared with controls, with a 4-year DFS of 83.3% versus 44.0% and a 4-year OS of 93.3% versus 60.2%. No infection-related fatality occurred postinduction, in contrast to 4% in Interfant-06. IVIg was administered in 19 (63%) patients, and G-CSF in five (17%). The mean Css of blinatumomab was 706 ± 194 pg/mL/d, and the median CL was 0.89 L/h/m2 (range, 0.57-2.66). Adding blinatumomab to standard treatment for infants with KMT2A-r ALL resulted in sustained improvement in outcome. Pharmacokinetics were comparable across pediatric age groups. The benefit of blinatumomab in frontline therapy remains promising and awaits further confirmation in ongoing trials.