Data from the phase 2/1b sub-study of the Beat AML Master Trial were presented at the 2021 American Society of Hematology (ASH) Annual Meeting and assessed the efficacy of gilteritinib monotherapy with the addition of decitabine in non-responders in older newly diagnosed FLT3-mutated acute myeloid leukemia (AML) patients having high and low variant allele frequency.

The primary endpoint was complete remission (CR) plus CR with incomplete blood count recovery (CRi) rate, and the response was assessed using modified 2017 ELN AML criteria.

“Gilteritinib is an oral potent selective FLT3 kinase inhibitor approved for marketing for the treatment of patients with relapsed/refractory (R/R) FLT3-mutated AML, but efficacy in older newly diagnosed FLT3-mutated AML pts is unknown. Furthermore, FLT3-mutations can be present as a dominant or subclone and impact of FLT3 inhibitor therapy in this setting is uncertain,” explained Elie Traer, MD, PhD, Oregon Health & Sciences University, Portland, Oregon, and colleagues.

A total of 19 patients were enrolled in the phase 2 component of the study and assigned to either dominant FLT3/Group 1 (GP1) or non-dominant FLT3/Group 2 (GP2). The median time on gilteritinib monotherapy was 3 cycles (1-18) in GP1 and 1 cycle (1-9) in GP2. The most common reasons for therapy discontinuation were therapy failure and relapse in GP1, and treatment failure and disease progression in GP2.

In phase 1b, 12 patients with no CR/CRi after up to 2 cycles of gilteritinib monotherapy were transferred to receive gilteritinib plus decitabine. The median total time on treatment (including gilteritinib monotherapy) was 4 cycles and median time on gilteritinib plus decitabine treatment was 3 cycles.

“Most common reasons for discontinuing treatment were progressive disease (33%) and treatment failure (25%); and 2 patients (17%) stopped treatment due to an adverse event (AE). Patients were treated with dose level 1 gilteritinib plus decitabine (n = 3), then dose level 2 gilteritinib plus decitabine (n = 9); only 1 patient had dose-limiting toxicity at dose level 2 (grade 3 hyperbilirubinemia and pneumonitis requiring steroid therapy), hence, dose level 2 gilteritinib plus decitabine was considered the maximum tolerated dose. CR plus CRi rate was 25 percent in 3 patients, all at dose level 2,” wrote Dr Traer and colleagues.

“In newly diagnosed patients ≥60 years old with dominant FLT3 AML, gilteritinib monotherapy induced a high 44 percent CR plus CRi rate and long median OS (21.7 mos). Patients with non-dominant FLT3 had low 10 percent CR plus CRi rate. Gilteritinib monotherapy was generally safe and was associated with differentiation syndrome in 1 patient. Concurrent gilteritinib plus decitabine was acceptably tolerated, only 1 patient had dose limiting toxicity, and the maximum tolerated dose was 120 mg/day gilteritinib plus decitabine. A subset of patients with no CR/CRi during gilteritinib monotherapy achieved remission with addition of decitabine. Based on these results, a triple combination treatment study with venetoclax is currently enrolling,” concluded Dr Traer and colleagues.

Elie T, Huang Y, Mims AS, et al. Gilteritinib (GILT) Monotherapy with Addition of Decitabine (DEC) in Non-Responders in Older Newly Diagnosed (ND) FLT3 Mutated Acute Myeloid Leukemia (AML) Patients Having High and Low Variant Allele Frequency (VAF): A Phase 2/1b Sub-Study of the Beat AML Master Trial. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 1277.