Analysis of Safety and Efficacy of Avapritinib As Targeted Therapy for Pediatric Acute Myeloid Leukemia Patients with KIT Mutation after Transplantation

Objective: To investigate the safety and efficacy of Avapritinib in pediatric acute myeloid leukemia (AML) with KIT mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: The clinical data of 6 AML patients with KITmutation and RUNX1::RUNX1T1 fusion gene positive in Children's Hospital of Soochow University were retrospectively analyzed, including 2 cases of KIT:N822K, 3 cases of KIT: exon17 and 1 case of KIT: Asp816Tyr. After achieving complete remission in morphology, allo-HSCT was performed. The clinical outcomes of prophylactic therapy (2/6) and preemptive intervention (4/6) with Avapritinib after complete stem cell engraftment were observed, and the adverse events during treatment were recorded.

Results: Adverse events occurred in 4 of the 6 patients, among whom neutropenia was the most common (4/6), followed by facial edema (2/6) and thrombocytopenia (1/6). 2 patients who received prophylactic treatment achieved morphological complete remission, and minimal residual disease (MRD), fusion gene and KIT mutations were all negative. 4 patients received preemptive intervention because of RUNX1::RUNX1T1 fusion gene turned positive after allo-HSCT, and 1 patient's RUNX1::RUNX1T1 turned negative after single-agent Avapritinib treatment for 2 months. 2 patients did not achieve continuous RUNX1::RUNX1T1 negative after preemptive therapy with Decitabine (DAC) and donor lymph infusion (DLI), and then was treated with Avapritinib, one's RUNX1::RUNX1T1 fusion achieved continuously negative after 1 month treatment of Avapritinib, the other's achieved continuous negative after 7 months treatment of Avapritinib. One patient was treated with Avapritinib after DAC and DLI as preemtive intervention, and RUNX1::RUNX1T1 fusion did not turn negative, but the relative value of RUNX1::RUNX1T1 fusion was lower than before and lived stable for more than 10 months.

Conclusions: Avapritinib is safe and effective in the prophylactic and preemptive treatment of AML with KIT mutation after allo-HSCT in children, which provides a clinical drug for the prevention of relapse after transplantation.