94P - Targeted therapy in pediatric acute myeloid leukemia: An unmet need

Background

Acute Myeloid Leukemia (AML) in children is rare with incidence of seven per million children annually. Recently a number of novel targeted therapies like FLT3 inhibitors, IDH inhibitors and BCL2 antagonists have been approved for adult AML. However conventional chemotherapy and allogenic stem cell transplantation remains the standard of care for pediatric AML. In the present study we analysed molecular genetics and their impact on induction outcome in paediatric AML patients.

Methods

This is a retrospective observational study. The study included newly diagnosed non M3 AML patients with age less than 18 years during 2018 and 2021. Age, gender, initial blood counts, FAB subtype of AML, molecular genetics, karyotype,-post induction bone marrow aspiration, MRD were analysed. All patients received standard 7+3 (Daunomycin+cytarbine) induction regimen.

Results

A total of 45 patients were evaluated. The median age at presentation was 13 years (range, 4-17 years) with male to female ratio of 1.5:1. Of these 45 patients, 11(24%) had t(8:21) abnormality, 6(13%) had NPM1 mutation without FLT3-ITD, 6(13%) patients had FLT3-ITD mutation, 3(6%) patients had inv(16), 3(6%) patients were positive for FLT3-TKD mutation and 16(35%) patients did not have any cytogenetic abnormality. Post induction marrow examination was complete remission, partial remission and persistence of disease in 25(56%), 11(24%) and 9(20%) patients respectively. Five (83%) out of 6 patients with FLT3-ITD and all FLT3 TKD mutation positive patients had persistence of disease (p<0.01). Post induction MRD was available in 14 patients. In all these 14 cases MRD correlated with bone marrow aspiration findings and all patients with CR had MRD negativity after induction. No mortality during induction was observed.

Conclusions

FLT3 mutations was observed in 19%{FLT3 ITD(13%), FLT3 TKD(6%)} of pediatric AML patients and appears to have an adverse impact on induction outcome in paediatric AML. FLT3 ITD/TKD inhibitors during induction have shown improved survivals in adult AML. With increasing incidence of pediatric AML in recent years, there is an unmet need to identify targeted and novel therapies for better outcomes in paediatric AML.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.