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

FLT3抑制剂治疗后急性髓系白血病中BCR-ABL1融合基因的出现:一种潜在的耐药靶点机制——病例系列研究

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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 prosurvival 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.

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