AUTHOR=Alotaibi Ahmad S. , Yilmaz Musa , Loghavi Sanam , DiNardo Courtney , Borthakur Gautam , Kadia Tapan M. , Thakral Beenu , Pemmaraju Naveen , Issa Ghayas C. , Konopleva Marina , Short Nicholas J. , Patel Keyur , Tang Guilin , Ravandi Farhad , Daver Naval 

TITLE=Emergence of BCR–ABL1 Fusion in AML Post–FLT3 Inhibitor-Based Therapy: A Potentially Targetable Mechanism of Resistance – A Case Series

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.588876

DOI=10.3389/fonc.2020.588876

ISSN=2234-943X

ABSTRACT=Despite the promising result with FLT3 inhibitors in AML, the emergence of resistance poses a significant challenge, leading to a shorter response duration and inferior survival. This is frequently driven by on-target or parallel pro-survival mutations. The emergence of BCR-ABL1 as a mechanism of possible clonal evolution in relapsed AML has rarely been reported. Here we report our experience with three patients who had emergent BCR-ABL1 fusion at relapse after FLT3 inhibitors-based therapies. The first patient was refractory to multiple lines of therapies, including FLT3 inhibitors-based therapy. Patients #2 and #3 showed some response to combined FLT3 inhibitor and BCR-ABL targeted therapy (gilteritinib and ponatinib). The availability of effective targeted therapies for BCR-ABL1 makes this an important aberration to proactively identify and possibly target at relapse post FLT3 inhibitor therapies.