Flumatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: An Open-Label, Multi-Center Study

Background Tyrosine kinase inhibitors (TKIs) ushered in the era of targeted therapy for chronic myeloid leukemia(CML), which greatly improved the prognosis of patients with CML. Flumatinib is a second-generation tyrosine kinase inhibitor (TKI), which is currently approved for patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in China. And some current clinical trials revealed that flumatinib has been shown to be a more potent inhibitor of BCR::ABL than imatinib.

Methods In this open label, single-arm, multicenter study, 127 patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML) treated with flumatinib were enrolled. The primary endpoint of this study was early molecular response (EMR) rates at 3 months. The secondary were the rates of complete cytogenic response (CCyR), major molecular response (MMR) at 3, 6, 12 months and treatment-related adverse events (AEs). The trial is registered with ClinicalTrials.gov NCT04591197.

Results From October 2020 to December 2022, a total of 158 patients with CP-CML were assessed for eligibility, of whom 127 were followed up for more than 3 months. 79(62%) patients were men and 48 (38%) were women. The median age was 47 years (range, 19-82 years), The median time from diagnosis to treatment was 6 days (0-176 days) and the median follow-up was 9.7 months (range 3.1-26.6 months). Of evaluable 127 patients, EMR was achieved by 85% (95% confidence interval [CI], 77.6%-90.7%) of patients at 3 months. After the initiation of flumatinib treatment, the incidence of MMR at 3, 6, and 12 months was 24%, 59%, and 73%, respectively. Patients receiving flumatinib had higher rates of CCyR at 6 months and MMR 12 months than the data from DASISION (dasatinib) and ENESTnd (nilotinib) therapy (85% vs 73% vs 67% and 73% vs 46% vs 44%). Progression-free survival (PFS) rate at 1-year was 97.2%. Diarrhea (34%) were the most commonly reported adverse events. Most treatment-related adverse events were grade 1/2. None of the patients discontinued or died due to AEs.

Conclusion Flumatinib as first-line therapy in patients with newly diagnosed CP-CML was not inferior to nilotinib and dasatinib and well tolerated.