Outcomes of Frontline Treatment Regimens for Patients With FLT3-Mutated AML

For patients with acute myeloid leukemia (AML) with an FLT3 mutation, treatments including an FLT3 inhibitor combined with standard chemotherapy and allogeneic stem cell transplantation combined with standard chemotherapy were associated with improved survival outcomes compared to standard therapy alone, according to results published in Cancer.

Previous research has identified FLT3 mutations, including internal tandem duplications (FLT3-ITD) and tyrosine kinase domain mutations (FLT3-TKD), are common in acute myeloid leukemia, with FLT3-ITD being associated with poorer outcomes. Researchers conducted a retrospective analysis to evaluate treatment outcomes among patients newly diagnosed with FLT3-mutated AML.

Overall, 619 patients with FLT3-mutated AML were included. For patients who received intensive chemotherapy and an FLT3 inhibitor had higher median relapse-free survival (RFS) compared to patients who did not take an FLT3 inhibitor (RFS, 32.3 vs 14.3 months; P= .055). A higher overall survival for patients who received an FLT3 inhibitor compared to those who did not (OS, median 35.5 vs FLT3 inhibitor 18.9 months; P = .098).

As for patients who underwent low-intensity treatment (LIT), a triplet regimen of LIT plus a FLT3i combined with venetoclax demonstrated a longer OS (19.1 months) compared with other LIT combinations (OS, 11.2 months with LIT alone, 9.2 months with LIT + FLT3i, and 10.3 months with LIT + venetoclax).

Among patients who had an FLT3-ITD mutation and a NPM1 mutation, an improved 2-year OS was observed (47% vs 33%; P = .087), regardless of treatment type. Landmark analyses demonstrated a strong survival benefit associated with allogeneic stem cell transplantation. In FLT3-ITD patients who received intensive chemotherapy, transplantation was associated with longer OS (52.6 vs. 22.7 months; P = .076). In the LIT cohort, allogeneic transplantation significantly improved OS (38.6 vs. 14.0 months; P < .0001).

“A FLT3i and allogeneic stem cell transplantation are key treatment modalities for patients who have FLT3-mutated AML,” the researchers concluded.

“LIT-based triplets are promising in IC-ineligible patients,” they added.

Source:

Bazinet A, Bataller A, Tapan Kadia, et al. A retrospective study of outcomes across time and treatment regimens in newly diagnosed, FMS‐like tyrosine kinase 3 (FLT3)‐mutated acute myeloid leukemia. Cancer. Published online March 17, 2025. doi:10.1002/cncr.35813