Real-World Outcomes of Patients with Refractory or Relapsed FLT3-ITD Acute Myeloid Leukemia: A Toulouse-Bordeaux DATAML Registry Study

Abstract

Two recent phase 3 trials showed that outcomes for relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) patients may be improved by a single-agent tyrosine kinase inhibitor (TKI) (i.e., quizartinib or gilteritinib). In the current study, we retrospectively investigated the characteristics and real-world outcomes of R/R FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML) patients in the Toulouse-Bordeaux DATAML registry. In the study, we included 316 patients with FLT3-ITD AML that received intensive chemotherapy as a first-line treatment. The rate of complete remission (CR) or CR without hematological recovery (CRi) was 75.2%, and 160 patients were R/R after a first-line TKI-free treatment (n = 294). Within the subgroup of R/R patients that fulfilled the main criteria of the QUANTUM-R study, 48.9% received an intensive salvage regimen; none received hypomethylating agents or low-dose cytarabine. Among the R/R FLT3-ITD AML patients with CR1 durations < 6 months who received intensive TKI-free treatment, the rate of CR or CRi after salvage chemotherapy was 52.8%, and these results allowed a bridge to be transplanted in 39.6% of cases. Finally, in this QUANTUM-R standard arm-matched cohort, the median overall survival (OS) was 7.0 months and 1-, 3- and 5-year OS were 30.2%, 23.7% and 21.4%, respectively. To conclude, these real-world data show that the intensity of the second-line treatment likely affects response and transplantation rates. Furthermore, the results indicate that including patients with low-intensity regimens, such as low-dose cytarabine or hypomethylating agents, in the control arm of a phase 3 trial may be counterproductive and could compromise the results of the study.

A Novel FLT3 Y842D Mutation Carriers a Potentially Highly Sensitivity to Midostaurin? Case Report and Literature Review

“…Generally, patients with mutant FLT3 frequently accompanied with hyperleukocytosis [15] . Nevertheless, the effect of each mutation form, particularly Y842D, on clinical phenotype remains to be clari ed.…”

Recent advances of targeted therapy in relapsed/refractory acute myeloid leukemia

“…However, 4.4% of patients received a low-intensity regimen as a salvage treatment in DATAML study, whereas about 25% of patients received LDAC treatment in the QUANTUM-R study. This maybe a major factor contribute to the difference in response rate and OS between two studies [ 43 ]. A recent study demonstrated that glucocorticoids (GCs) enhance the antileukemic activity of FLT3 inhibitors in FLT3-mutant acute myeloid leukemia.…”

Mechanisms of Resistence of New Target Drugs in Acute Myeloid Leukemia

“…The Median OS of 7 months observed in the French study was also superior to the Quantum-R OS of 4.7 months. The authors argue that the possible bias, caused by the inclusion in the control arm of patients receiving low-intensity regimens, such as low-dose cytarabine or hypomethylating agents, might compromise the results of similar phase 3 trials [17].…”