[Efficacy and safety analysis of avapritinib in children with RUNX1::RUNX1T1 positive-acute myeloid leukemia with KIT mutations].

Objective

To evaluate the efficacy and safety of avapritinib in children with RUNX1::RUNX1T1-positive acute myeloid leukemia (AML) with KIT mutations.

Methods

Clinical data on children with RUNX1::RUNX1T1-positive AML with KIT mutations who received avapritinib at the Department of Pediatrics, Peking University People's Hospital, from September 2022 to June 2025 were collected. The overall response rate (ORR), event-free survival (EFS), overall survival (OS), and adverse reactions of avapritinib treatment were retrospectively analyzed.

Results

Ten children (6 males, 4 females) with a median age of 6.5 years were enrolled. All carried KIT mutations (D816V, n=8; D816H, n=1; D816Y, n= 1). All children completed ≥1 cycle of avapritinib; 9 received ≥2 cycles, and 6 received ≥3 cycles. After cycle 1, the ORR was 80% (8/10), with 5 children achieving ≥1 log reduction in RUNX1::RUNX1T1. The ORR was 78% (7/9) after cycle 2 and 67% (4/6) after cycle 3. With a median follow-up of 10 months, the EFS rate were 90%, and the OS rate was 100%. During avapritinib treatment, 5 of the 10 children showed elevated levels of the RUNX1::RUNX1T1. During combination avapritinib and chemotherapy, adverse events were largely attributable to chemotherapy, manifesting as hematological adverse reactions, gastrointestinal reactions, and infections, all of which improved after symptomatic treatment. When avapritinib was used alone or with interferon, toxicity was mainly associated with grade 1-2 hematological adverse reactions; one case developed convulsions and improved after drug withdrawal and symptomatic treatment.

Conclusion

Avapritinib provides a favorable initial response in children with RUNX1::RUNX1T1-positive AML harboring KIT mutations, enabling deeper molecular remission; however, response rates decline with prolonged treatment. Avapritinib has a favorable safety profile.