Crenolanib–Chemo Combo Improves Outcomes in Newly Diagnosed, FLT3-Mutated AML

San Diego, California—A crenolanibchemotherapy improved overall outcomes in patients with newly diagnosed acute myeloid leukemia (AML) that is positive for the FLT3 mutation and other co-occurring driver mutations, according to results from a recent study presented by Aaron D. Goldberg, MD, PhD, Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, at the 2018 ASH Annual Meeting.

Poor clinical outcomes have been associated with FLT3 mutations in patients with AML. Similarly, other driver mutations that frequently co-occur with FLT3 mutations (eg, NPM1 with DNMT3A, WT1, and RUNX1) are linked with poor prognoses in this population.

“Crenolanib is a highly potent and specific type-I FLT3 inhibitor, which has shown promising safety and efficacy in combination with chemotherapy,” explained Dr Goldberg and colleagues, who conducted a trial examining crenolanib plus chemotherapy in 44 patients with newly diagnosed FLT3-mutated AML.

All patients received 7+3 induction chemotherapy plus crenolanib, consolidation with high-dose cytarabine plus crenolanib, and/or allogeneic stem cell transplantation HCT followed by crenolanib maintenance therapy in this study. Sequencing was performed at baseline for 36 of these patients.

As of the data cutoff of July 25, 2018, the median survival follow-up for these patients was 20.7 months. The investigators carried out a post-hoc analysis to evaluate the effect of patient genomic profile on outcomes using data from the German-Austrian AML Study Group as a historical control.

A total of 10 patients had co-occurring FLT3-ITD, NPM1, and DNMT3A mutations; Dr Goldberg and colleagues observed improved overall survival with crenolanib therapy in these patients versus historical controls. Likewise, outcomes were significantly improved with crenolanib therapy in the 6 patients who had FLT3-ITD and WT1 mutations.

Improved overall survival was also seen in the 10 patients with FLT3 (ITD or TKD) and RUNX1 mutations.

“This analysis suggests that adding a potent pan-FLT3 inhibitor can overcome the poor prognostic implication of adverse mutations co-occurring with mutated FLT3,” Dr Goldberg and colleagues stated, adding that the findings also support the use of crenolanib plus chemotherapy to improve overall outcomes in patients with FLT3-mutated AML with diverse mutational profiles.

“[A] randomized trial has been initiated of standard chemotherapy combined with either crenolanib or midostaurin in newly diagnosed patients with FLT3-mutant AML,” they concluded.—Hina Khaliq

Goldberg AD, Collins RH, Stone RM, et al. Addition of crenolanib to induction chemotherapy overcomes the poor prognostic impact of co-occurring driver mutations in patients with newly diagnosed FLT3-mutated AML. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 1436.

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