结合人口学特征比较国产和原研伊马替尼治疗慢性髓性白血病慢性期患者的有效性和安全性

Comparison of the efficacy and safety of Chinese generic imatinib and branded imatinib in patients with chronic myeloid leukemia in consideration of demographic characteristics

目的比较国产和原研伊马替尼一线治疗慢性髓性白血病慢性期(CML-CP)患者的有效性和安全性;探索服用原研伊马替尼获得完全细胞遗传学反应(CCyR)后转换为国产伊马替尼的患者疾病的稳定性和不良反应的变化。方法①一线治疗组:回顾性收集和分析2013年10月至2018年8月期间,接受国产仿制伊马替尼(商品名昕维^®)或进口原研伊马替尼(商品名格列卫^®)作为一线治疗并定期随访、监测的CML-CP连续病例。②转换组:回顾性收集和分析2006年12月至2016年9月期间,接受原研伊马替尼至少获得CCyR后转换为国产仿制伊马替尼治疗的CML-CP连续病例。结果①一线治疗组:共409例(国产伊马替尼201例,原研伊马替尼208例)患者入组,中位年龄42(18~83)岁。国产和原研组患者人口学特征差异具有统计学意义:国产伊马替尼组患者中受教育水平更低(P<0.001)、离异或丧偶者比例更高(P=0.004)、农村户籍者比例更高(P<0.001)。两组年龄、性别、Sokal危险度评分、WBC和HGB水平的差异无统计学意义。中位随访25(3~62)个月,国产伊马替尼组和原研伊马替尼组的3年CCyR、主要分子学反应(MMR)、分子学反应4.0(MR4.0)和分子学反应4.5(MR4.5)的累积获得率差异均无统计学意义(97.5%对94.5%,P=0.592;84.3%对93.1%,P=0.208;42.7%对41.7%,P=0.277;25.4%对33.0%,P=0.306),3年无失败生存(FFS)率、无进展生存(PFS)率和总生存(OS)率差异亦无统计学意义(76.7%对81.0%,P=0.448;91.8%对96.3%,P=0.325;95.8%对98.5%,P=0.167)。多因素分析显示,TKI类型不影响患者的治疗反应(CCyR、MMR、MR4.0和MR4.5累积获得率)及结局(FFS、PFS和OS)。两组不良反应发生率也相似。②转换组:共39例患者入组,中位年龄42(23~80)岁,于原研伊马替尼中位治疗38(8~114)个月后换为国产伊马替尼,换药后中位随访39(6~63)个月,23例(58.9%)患者分子学反应维持原来水平,12例(30.8%)分子学反应改善。新发药物不良反应均可耐受。结论人口学特征影响CML-CP患者的用药选择。在规范的监测和管理下,国产与原研伊马替尼一线治疗CML-CP患者的有效性和安全性相当。对于接受原研伊马替尼后获得稳定治疗反应的患者,可有效、安全地转换为国产伊马替尼。

Objectives To compare the efficacy and safety of Chinese generic imatinib with branded imatinib as frontline therapy in adults with newly diagnosed chronic myeloid leukemia in chronic phase(CML-CP)(Frontline group),and to explore the efficacy and safety of Chinese generic imatinib in CML-CP patients switching from branded imatinib(Switching group).Methods Frontline group:Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib(Xinwei^®)or branded imatinib(Glivec^®)between October 2013 and August 2018 were retrospectively collected and analyzed.Switching group:Data of adults diagnosed with CML-CP who received branded imatinib and then switched to Chinese generic imatinib after achieving at least complete cytogenetic response(CCyR)were retrospectively collected and analyzed.Results Frontline group:In total,409 adult patients receiving Chinese generic imatinib(n=201)or Glivec(n=208)were included in this study.Median age was 42 years(range,18-83 years).Comparison of baseline showed significant difference on demographic characteristics among two cohorts:lower education level(P<0.001),and divorced or widowed status(P=0.004)and rural household registration(P<0.001)were more common in the generic imatinib cohort than those in the Glivec cohort.There was no significant difference on age,gender,Sokal risk score,WBC and HGB between the 2 cohorts.With a median follow-up of 25 months(range,3-62 months),there was no significant difference on the 3-year cumulative incidence of achieving CCyR(97.5%vs 94.5%,P=0.592),major molecular response(MMR)(84.3%vs 93.1%,P=0.208),molecular response^4.0(MR^4.0)(42.7%vs 41.7%,P=0.277),molecular response^4.5(MR^4.5)(25.4%vs 33.0%,P=0.306)as well as the 3-year probabilities of failure free survival(FFS)(76.7%vs 81.0%,P=0.448),progression free survival(PFS)(91.8%vs 96.3%,P=0.325)and overall survival(OS)(95.8%vs 98.5%,P=0.167)between the generic and branded imatinib cohorts.Multivariate analysis showed the type of imatinib was not associated with treatment responses and outcomes.The incidences of adverse effects were comparable in the 2 cohorts.Switching group:In total,39 patients switching from branded imatinib to Chinese generic imatinib after achieving at least CCyR were included in this study.Median age was 42 years(range,23-80 years).With a median follow-up of 39 months(range,6-63 months),molecular responses were maintained in 23(58.9%)patients and improved in 12(39.8%)patients.Adverse effects were tolerable.Conclusion Demographic characteristics might influence the choice of the type of TKI used in CML-CP patients.There was a comparable efficacy and safety between the Chinese generic imatinib and the branded imatinib in adults with newly diagnosed CML-CP under standard management and closely monitoring.Patients could safely switch from the branded imatinib to the Chinese generic imatinib.