Sustained Benefit of Blinatumomab in Infants With KMT2A-Rearranged ALL: Long-Term Outcomes, Toxicity, and Pharmacokinetics
Mené sur 30 enfants atteints d'une leucémie lymphoblastique aiguë avec réarrangements au niveau du gène KMT2A (durée médiane de suivi : 4,2 ans), cet essai évalue l'efficacité, du point de vue de la survie sans maladie et de la survie globale, et la toxicité de l'ajout de blinatumomab à une chimiothérapie puis examine ses caractéristiques pharmacocinétiques
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.
Journal of Clinical Oncology , article en libre accès, 2026