Induction therapy with combination chemotherapy plus gilteritinib yielded an excellent compositive complete remission (CRc) rate with no treatment-related deaths in patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML), according to the results of the phase II Precog 0905 study, which will be presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition.
However, although gilteritinib increased CRc compared with the study comparative midostaurin, it did not significantly increase the FLT3 mutation-negative CRc rate after induction, noted study researchers, led by Selina Luger, MD, of Abramson Cancer Center at the Hospital of the University of Pennsylvania in Philadelphia.
Dr. Luger and colleagues conducted the study, which compared clearance of FLT3 mutation with the use of intensive chemotherapy plus either oral multi-kinase inhibitor midostaurin or FLT3 inhibitor gilteritinib.
Gilteritinib was approved by the U.S. Food and Drug Administration in 2018 for the treatment of relapsed or refractory AML with FLT3 mutation.
The study included 180 patients with newly diagnosed AML with centrally detected FLT3 mutations. All patients received induction therapy with cytarabine infusion on day 1-7 and daunorubicin on day 1-3. Patients were randomly assigned to gilteritinib 120 mg daily or midostaurin 50 mg twice daily on days 8-21. Consolidation included 60 days of induction with cytarabine and gilteritinib or midostaurin. Patients could go to transplant at any time.
The primary endpoint of the study was FLT3-mutated measurable residual disease (MRD)-negative CRc after induction. Included patients had AML with either FLT3-ITD or -TKD mutations; FLT3-ITD was present in 80% of the gilteritinib arm and 78.2% of the midostaurin arm.
Significantly more patients assigned to gilteritinib achieved CRc compared with midostaurin (85.6% vs. 72.4%; p=0.042). After induction, the rate of FLT3-mutated MRD-negative CRc was not significantly different at 40% for patients assigned gilteritinib compared with 47.1% for midostaurin (p=0.366).
Using flow cytometry, MRD-negative CRc was found in 64.4% of patients assigned to gilteritinib compared with 59.8% assigned to midostaurin.
The researchers conducted an exploratory analysis and found that 66% of patients assigned to gilteritinib ultimately proceeded to transplant in first remission compared with 46% of patients assigned midostaurin. Additionally, looking at mutation status after consolidation cycle 1, more patients assigned gilteritinib converted from FLT3 mutation positivity to FLT3 mutation negativity after induction (83% vs. 44.4%).
No treatment-related deaths were reported in either arm.
The full study is scheduled to be presented on Saturday, December 7, 2024, at 3:00 p.m. at the 66th ASH Annual Meeting and Exposition in San Diego. This article will be replaced with a summary of the presentation after the session has concluded. Check back later this month for updates!
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Luger S, Chen L, Pratz KW, et al. Gilteritinib results in higher remission and transplant rates than midostaurin but does not increase the post-induction mutational MRD negative rate: results of the phase 2 randomized Precog 0905 study in newly diagnosed FLT3 mutated AML. Abstract 221. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7, 2024; San Diego, California.
