Chronic myeloid leukemia (CML) is a common blood cancer. Most CML patients can control their condition using tyrosine kinase inhibitor (TKI) drugs. Since the advent of imatinib, long-term survival rates for CML patients have significantly improved.As the primary treatment drug, imatinib yields excellent results for most newly diagnosed CML patients. However, after a period of treatment, due to individual variations among patients, some CML patients may develop resistance to TKIs. Medical clinical research data indicates that for the first-generation tyrosine kinase inhibitor (TKI) imatinib, the resistance rate reaches 15–25% and continues to rise annually.Medical experts indicate that the current resistance observed in CML patients stems partly from genetic mutations and partly from dysfunction in the supporting cells of hematopoietic stem cells within the bone marrow.
The leukemia stem cells present in CML patients are a type of "runaway" hematopoietic stem cell. They replicate uncontrollably and abnormally actively, producing large quantities of leukemia cells. An excess of these cells impairs normal hematopoietic functions and other bodily processes, thereby causing leukemia.While commonly used tyrosine kinase inhibitors (TKIs) effectively suppress the proliferation of mature CML cells actively multiplying, they cannot completely eliminate these leukemic stem cells. Even patients achieving treatment-free remission and discontinuing medication remain at risk of relapse.
Drug resistance in CML patients is typically assessed through three key indicators: complete blood count (CBC) abnormalities, Ph chromosome detection, and Bcr-Abl fusion gene levels. Resistance manifests as failure to achieve remission, the need for lifelong medication after remission, or recurrence of the fusion gene after initial negativity.
Medical experts indicate that after one year of first-generation drug therapy, most CML patients exhibit a decrease in corresponding indicators and a reduction in viral load. However, if a patient's blood counts remain abnormal, the Ph chromosome remains detectable, and the Bcr-Abl fusion gene count remains high, clinical assessment will determine drug resistance.
In recent years, medical advances and ongoing research have expanded targeted therapy options for the BCR-ABL fusion gene. Beyond imatinib, patients now have access to nilotinib, dasatinib, and newer TKIs with enhanced inhibitory potency. With appropriate medication selection under specialist guidance, many CML patients can achieve favorable treatment outcomes.
Launched in late 2019, flumatinib mesylate (Haosen XinFu) is China's first domestically developed second-generation TKI. It was included in China's first-line treatment regimen for CML in May this year.It is reported that flumatinib mesylate (Haosen XinFu) is a small-molecule protein tyrosine kinase inhibitor. It primarily inhibits Bcr-Abl tyrosine kinase activity, thereby suppressing tumor cell proliferation in Philadelphia chromosome-positive CML patients and some acute lymphoblastic leukemia patients, and inducing tumor cell apoptosis.
Furthermore, the review report for flumatinib mesylate tablets (Haosen XinFu) published by the CDE as early as March this year fully affirmed flumatinib's superior efficacy and safety profile compared to imatinib.
In first-line therapy, patients treated with flumatinib demonstrated significantly higher major molecular response (MMR) rates at 6 and 12 months compared to imatinib, offering substantial benefits for disease progression and eventual discontinuation of treatment.Additionally, flumatinib demonstrated substantial advantages over imatinib in managing common adverse reactions such as edema, limb pain, and rash, as well as hematologic toxicities like neutropenia and anemia. It represents a new therapeutic option for patients with imatinib-resistant CML.