Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups.

Simple Summary: Relapsed/refractory FLT3-mutated acute myeloid leukemia (AML) is associated with a poor prognosis. Mutations in the FLT3 gene provide a target for therapeutic intervention. Two FLT3 inhibitors, gilteritinib and quizartinib, when used as single agents, have demonstrated efficacy in this context. The aim of our retrospective study was to compare the outcomes of 50 patients diagnosed with FLT3-mutated AML treated with gilteritinib or quizartinib monotherapy, with results from phase 3 clinical trials and with other real-world studies. Despite differences among the cohorts, our findings confirm that gilteritinib and quizartinib monotherapy represent effective and tolerable treatment options for patients with relapsed/refractory FLT3-mutated AML in real-world settings, with response and toxicity rates consistent with those reported in prior studies. Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3^mut) have a dismal prognosis. FLT3^mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3^mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. Results: The median age was 62.5 years, and 52% were women. Most patients presented with FLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3^mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population. [ABSTRACT FROM AUTHOR]