氟马替尼治疗慢性髓性白血病慢性期患者的临床疗效及安全性分析

Clinical Efficacy and Safety of Flumatinib in the Treatment of Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase

目的:探讨国产新药甲磺酸氟马替尼对初诊慢性髓性白血病慢性期(CML-CP)患者的临床疗效及安全性。方法:收集2020年3月1日至2022年3月31日西南医科大学附属医院血液内科收治的32例成人初诊未经过除羟基脲外其他任何抗CML治疗的CML-CP患者,给予甲磺酸氟马替尼600 mg,1/d,口服,评估治疗3、6、12个月时患者的血液学、细胞遗传学和分子学反应及安全性。结果:治疗≥3个月的患者31例,治疗≥6个月的患者24例,治疗≥12个月的患者14例。治疗3个月时,31例患者中30例获得完全血液学反应(CHR);24例患者进行了细胞遗传学检测,获得主要遗传学反应(MCyR)22例,其中21例获得完全细胞遗传学反应(CCyR);25例患者进行了分子学检测,BCR-ABLIS≤10%的患者22例,其中10例BCR-ABLIS≤0.1%,6例BCR-ABLIS≤0.01%。治疗6个月时,24例患者中23例获得CHR;17例进行了细胞遗传学检测,全部获得CCy R;23例进行了分子学检测的患者中20例BCR-ABLIS≤1%,其中16例BCR-ABLIS≤0.1%,12例BCR-ABLIS≤0.01%。治疗12个月时,14例患者全部获得CHR和CCy R;10例BCR-ABLIS≤0.1%,其中9例BCR-ABLIS≤0.01%。Ⅲ-Ⅳ级白细胞减少、血小板减少及贫血发生率分别为13.3%、20.0%和3.3%,有1例患者因氟马替尼治疗1月内发生严重而持久的血液学不良反应而停药。主要的非血液学不良反应依次为肝功能异常(20.0%)、腹泻(10.0%)、骨关节疼痛(10.0%)、肌肉痉挛(6.7%)、皮疹(6.7%)、肾功能损害(6.7%)、恶心(3.3%),多为Ⅰ-Ⅱ级,无患者发生Ⅳ级非血液学不良反应。无药物毒性相关性死亡。结论:国产新药甲磺酸氟马替尼一线治疗初诊CML-CP能够使患者早期、快速获得深层分子学反应和细胞遗传学反应,且安全性良好。

Objective:To explore the clinical efficacy and safety of flumatinib mesylate produced in China in patients with newly diagnosed chronic myeloid leukemia in chronic phase(CML-CP).Methods:32 newly diagnosed CML-CP patients admitted to the Hematology Department of the Affiliated Hospital of Southwest Medical University from March 1,2020 to March 31,2022,who had never received any tyrosine kinase inhibitor(TKI)were included in the study.The patients were treated by flumatinib mesylate 600mg once daily.The hematologic,cytogenetic and molecular responses were assessed at 3-,6-and 12-month,and adverse effects of the drug were evaluated.Results:31 patients were treated with flumatinib for≥3 months,of which 24 patients were treated for≥6 months and 14 patients were treated for≥12 months.At 3rd month of treatment,30 out of 31 patients achieved complete hematologic response(CHR);24 patients underwent cytogenetic testing and 22 cases achieved major cytogenetic response(MCyR),of which 21 cases achieved complete cytogenetic response(CCyR);Among 25 patients who underwent molecular testing,22 patients had BCRABLIS≤10%,including 10 patients with BCR-ABLIS≤0.1%,and 6 patients with BCR-ABLIS≤0.01%.At 6th month of treatment,23 out of 24 patients achieved CHR;17 patients underwent cytogenetic testing and all achieved CCyR;Among 23 patients who underwent molecular testing,20 patients had BCR-ABLIS≤1%,including 16 patients with BCR-ABLIS≤0.1%and 12 patients with BCR-ABLIS≤0.01%.At 12nd month of treatment,all 14 patients achievedCHR and CCyR;Among them,10 patients had BCR-ABLIS≤0.1%,including 9 patients with BCR-ABLIS≤0.01%.ThegradeⅢ/Ⅳleukopenia,thrombocytopenia and anemia rates in the patients were 13.3%,20.0%and 3.3%,respectively.One patient stopped flumatinib therapy due to severe and persistent hematologic toxicity.The major non-hematologicadverse events were abnormal liver function(20%),diarrhea(10%),bone/joint pain(10%),muscle spasm(10%),rash(6.7%),acute kidney injury(6.7%)and nausea(3.3%),most of which were grade I-II.No patient experienced gradeⅣnon-hematologic adverse events.No drug toxicity-related death occurred.Conclusion:Flumatinib mesglate,as the firstlinetreatment for newly diagnosed CML-CP,can enable the patients to achieve early and deep molecular and cytogeneticresponses,and shows good safety.