Therapy for relapsed/refractory disease…Targeted therapy:…Therapy for AML with FLT3-TKD mutation...Gilteritinib (category 1)

Baseline FLT3 mutations in the gilteritinib vs SC groups were: FLT3-ITD (91.4% vs 83.1%), FLT3-TKD (6.0% vs 11.9%), and both FLT3-ITD and FLT3-TKD (2.6% vs 5.1%). Median OS follow-up duration was 11.1 mo for gilteritinib and 6.9 mo for SC. Median OS was longer with gilteritinib (9.0 mo) vs SC (4.7 mo; HR 0.549 [95% CI: 0.379, 0.795]; P=0.00126); 1-year survival rate was 33.3% and 23.2%, respectively. OS benefit was seen with gilteritinib vs SC across most subgroups (Figure). Pts on gilteritinib had longer EFS than pts on SC (median EFS 2.8 vs 0.6 mo; HR 0.551 [95% CI: 0.395, 0.769]; P=0.00004). More pts had CR on gilteritinib (16.4%) vs SC (10.2%; P=0.17690); CRc rates were 50.0% and 20.3% (P<0.00001). Gilteritinib significantly prolonged OS and EFS vs SC in pts with R/R FLT3mut+ AML in Asia.

All patients had an AML diagnosis with a FLT3 mutation…Of the 40 patients included in this study, 30 (75%) had the FLT3-ITD mutation, and 10 (25%) had the FLT3-TKD mutation….Post-HSCT maintenance, primarily with gilteritinib, resulted in improved OS and RFS in our patients. Amongst our patients receiving FLT3 inhibitors for maintenance, OS at 24 months was 96.2% and RFS was 89.7%.

We studied to the combination of gilt with the CLIA regimen in FLT3 mutated AML....16 pts (67%) achieved complete remission (CR), 2 (8%) had CR with incomplete recovery (CRi), for a CR/CRi rate of 75%. 13 responding pts (54%) underwent to allogeneic SCT. The median overall survival for the entire cohort was not reached....The combination of the FLT3 inhibitor gilteritinib to CLIA produced high rates of complete remission in pts diagnosed with FLT3-mutated AML.

Gilteritinib had a favorable safety profile and generated potent FLT3 inhibition leading to high rates of antileukemic responses in patients with FLT3mut+ R/R AML….our study both confirms that FLT3 is a high-value target in R/R AML and demonstrates that long-term success of therapeutic FLT3 inhibition is optimized by agents with potent, selective, and sustained activity against FLT3-ITD mutations as well as TKD mutations.