At the 59th American Society of Hematology (ASH) Annual Meeting, Atlanta, GA, Eunice S. Wang, MD, from Roswell Park Cancer Institute, Buffalo, NY, presented results from a phase II trial, which assessed the tolerability and efficacy of crenolanib, a highly selective type I tyrosine kinase inhibitor of FLT3, in combination with standard induction chemotherapy in newly diagnosed FLT3-mutated AML patients ≤ 60 years old.
In total, 44 patients ≤ 60 years with newly diagnosed FLT3-mutated AML were enrolled in this trial. Patients were administered standard chemotherapy (cytarabine [100 mg/m2 for 7 Days] and either daunorubicin [90 mg/m2] or idarubicin [12 mg/m2] for 3 Days) in combination with crenolanib (100 mg TID was administered continuously starting on Day 9 of chemotherapy cycle). The results from 29 patients treated in this phase II study were reported.
- Most common treatment-emergent AEs regardless of attribution in ≥ 15% patients include nausea (52%), diarrhea (52%), vomiting (41%) and maculopapular rash (38%)
- Overall CR/CRi rate: 83% (24/29)
- FLT3 status after treatment in evaluable patients (n = 23) in CR/CRi
- FLT3 mutation clearance was seen in 91% (21/23) of patients including patients who had variant FLT3 mutations
- 9% (2/23) of patients remained FLT3 positive
MRD was measured by multi-parameter flow cytometry in bone marrow samples in CR/CRi patients (n = 16) at count recovery.
- 94% of patients (n = 16) in CR/CRi achieved MRD negative status after one cycle of cytarabine/anthracycline/crenolanib therapy
In total, 22 patients received consolidation therapy consisting of high-dose cytarabine plus crenolanib (n = 18), allo-HSCT (n = 15) and crenolanib maintenance (n = 13)
- After a median follow-up of 15.9 months, the CIR was 16%
- After a median follow-up of 17.6 months, OS was 79%
- A total of six deaths occurred during relapse (n = 2), refractoriness (n = 2) and remission (n = 2)
In an interview with the AGP, the speaker, Eunice Wang, discussed the findings of this phase II study where she highlighted that crenolanib in combination with standard induction and consolidation chemotherapy was “extremely well tolerated” and induced a “very good” response in patients ≤ 60 years with de novo FLT3 mutant AML.
Based on the findings of this phase II study, a phase III randomized study (NCT03258931) which is comparing the efficacy of crenolanib versus midostaurin in combination with standard induction and consolidation chemotherapy in newly diagnosed AML patients with FLT3 mutation is scheduled to start accrual in early 2018”. The primary endpoint of this study is Event Free Survival (EFS).