Pb1724: nilotinib plus chemotherapy in pediatrics with philadelphia chromosome-positive acute leukemia: a single center experience

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Despite significant improvements in the prognosis of dasatinib plus multi-agent chemotherapy for pediatric Philadelphia chromosome-positive (Ph-positive) acute leukaemia, there are still about 19.8% of subsequent relapses and 11.8% of disease-related deaths, which are associated with poor survival and quality of life. Moreover, dasatinib-induced side effects occur, some pediatric Ph-positive ALL patients are intolerant to standard therapy and may leukaemia progression from delaying chemotherapy. Nilotinib is a second-generation tyrosine kinase inhibitor approved by the FDA for the treatment of pediatrics with Ph-positive chronic myelogenous leukaemia. The combination of nilotinib with chemotherapy was reported effective for adults with Ph-positive ALL in phase 2 studies, but evidence of efficacy and safety among pediatrics with Ph-positive acute leukaemia is still lacking. Aims: To investigate the efficacy and safety of nilotinib (230mg/m2 twice a day) with chemotherapy in BCR-ABL1-positive or dasatinib-intolerant pediatric Ph-positive acute leukaemia patients in a real-world setting. Methods: This is a retrospective, observational study including BCR-ABL1-positive or dasatinib-intolerant pediatric patients aged < 18 years with Ph-positive acute leukaemia while complete response achieved after induction therapy during the period 2020-2023. Nilotinib was administered 230mg/m2 twice a day with standard chemotherapy. Molecular response and adverse events were assessed. The deep molecular response is defined as BCR-ABL1 values of ≤ 0.01% on the international reporting scale. Results: Eleven Ph-positive patients were included in this study with a median age of 7 (range, 2-11 years) years, including ten cases of acute lymphoblastic leukaemia and one mixed phenotype acute leukaemia. Nilotinib was applied for BCR-ABL1-positive (> 0.01%, n = 3) or dasatinib-intolerant (n = 8) cases. 8 patients discontinued dasatinib due to gastrointestinal bleeding and hydrothorax. All patients achieved deep molecular response after nilotinib-based therapy. The median follow-up time was 10.7 (range, 0.5-33.6) months and all 11 patients remained on continuation therapy. No febrile neutropenia, infection or grade ≥ 3 non-hematologic adverse events occurred when nilotinib administered. Summary/Conclusion: Our study evaluated the use of nilotinib in combination with chemotherapy in pediatrics with Ph-positive acute leukaemia. These promising results suggest nilotinib based therapy was safe and resulted in deep molecular responses in pediatric Ph-positive acute leukaemia with BCR-ABL1-positive and dasatinib intolerance, although long-term follow-up is still needed.Keywords: Nilotinib, Philadelphia chromosome, Acute leukemia, Pediatric