Outcomes with sequential FLT3-inhibitor-based therapies in patients with AML.

ABSTRACT:

Background

Second-generation FLT3-inhibitors (FLT3i) demonstrated single-agent composite CR rates (CRc) of 45-55% in patients with relapsed/refractory (R/R) FLT3-mutated AML in phase II/III trials. However, >?85% of patients treated were prior FLT3i naïve. The response rates to sequential FLT3i exposure remain poorly defined.

Methods

We retrospectively reviewed patients with FLT3-mutated AML between November 2006 and December 2019.

Results

In frontline patients treated with a FLT3i (cohort 1), the CRc rates and median overall survival (OS) with the first (n?=?56), second (n?=?32), and third FLT3i-based (n?=?8) therapy were 77%, 31%, and 25%, and 16.7 months, 6.0 months, and 1.4 months, respectively. In patients receiving a FLT3i-based therapy for the first time in a R/R AML setting (cohort 2), the CRc rates and median OS were 45%, 21%, and 10%, and 7.9 months, 4.0 months, and 4.1 months with the first (n?=?183), second (n?=?89), and third/fourth (n?=?29) FLT3i-based therapy, respectively. In cohort 1, CRc rates with single-agent FLT3i (n?=?21) versus FLT3i-based combinations (n?=?19) in second/third sequential FLT3i exposures were 19% versus 42%, respectively. In cohort 2, the CRc rates with single-agent FLT3i (n?=?82) versus FLT3i-based combinations (n?=?101) in first FLT3i exposure were 34% versus 53%, respectively, and those with single-agent FLT3i (n?=?63) versus FLT3i-based combinations (n?=?55) in second/third/fourth sequential FLT3i exposures were 13% versus 25%, respectively.

Conclusion

CRc rates drop progressively with sequential exposure to FLT3i's in FLT3-mutated AML. In all settings, CRc rates were higher with FLT3i-based combinations compared with single-agent FLT3i therapy in similar FLT3i exposure settings.

SUBMITTER: Yilmaz M 

PROVIDER: S-EPMC7542942 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature