Real-world efficacy and adverse events of frontline nilotinib in pediatric chronic myeloid leukemia in chronic phase: A prospective multicenter study from SCCCG[PLUS]-CML 2023.

[BACKGROUND] Chronic myeloid leukemia (CML) is rare in children and often shows more aggressive features than in adults. Real-world data on the efficacy and safety of frontline nilotinib in pediatric CML in chronic phase (CML-CP) remain limited.

[METHODS] This prospective multicenter real-world study evaluated the efficacy, safety, and pharmacokinetics of frontline nilotinib in newly diagnosed pediatric CML-CP across 26 hospitals in China between January 2023 and April 2025. Patients received nilotinib 230 mg/m twice daily. Primary end points were complete cytogenetic response (CCyR) at six cycles and major molecular response (MMR) at 12 cycles. Secondary end points included time to MMR, event-free survival (EFS), and safety.

[RESULTS] Among 59 enrolled patients (median age, 10.6 years), 71.8% (28/39) achieved MMR at 12 cycles and all achieved CCyR at six cycles. Median time to MMR was 6.2 (3.3, 12.2) months, and 2-year EFS was 93.3% (84.4%-100%). Nilotinib trough concentrations (Ctrough) correlated negatively with BCR::ABL1 transcript levels at cycles 6 and 12. Patients with Ctrough >950 ng/mL were three to five times more likely to reach MMR, whereas those with Ctrough ≥1500 ng/mL had a 6.5-fold higher risk of hyperbilirubinemia.

[CONCLUSIONS] Frontline nilotinib thus shows strong efficacy and manageable safety in pediatric CML-CP. Higher drug exposure predicts deeper molecular responses but increases toxicity, supporting the potential role of therapeutic drug monitoring.