维奈克拉联合阿扎胞苷治疗老年初治急性髓系白血病的临床分析

Clinical analysis of venetoclax combined with azacitidine in elderly patients with newly diagnosed acute myeloid leukemia

目的:探讨维奈克拉联合阿扎胞苷方案在老年初治急性髓系白血病(acute myeloid leukemia,AML)患者中的疗效以及安全性。方法:回顾性分析2020年9月至2021年12月在空军军医大学第二附属医院接受维奈克拉联合阿扎胞苷方案治疗的27例老年初治AML患者的临床资料,观察患者的完全缓解/完全缓解伴血液学不完全恢复(complete remission/complete remission with incomplete hematological recovery,CR/CRi)率、总体有效率(overall response rate,ORR)及微小残留病(minimal residual disease,MRD)转阴率,分析影响患者疗效和预后的因素,并评估该方案的安全性。结果:27例患者的中位疗程数为3(1~9)个,CR/CRi率为51.9%(14/27),ORR为63.0%(17/27),其中44.4%的患者在1个疗程后即达到CR/CRi。14例CR/CRi患者中的9例(64.3%)在1~2个疗程治疗后MRD转阴。年龄≥70岁(P=0.035)、初诊血红蛋白≥80 g/L(P=0.028)、合并ASXL1突变(P=0.015)及未合并TP53突变(P=0.039)的患者可获得更好的治疗反应。中位随访10.8(0.9~29.6)个月,中位OS时间未达到,1年OS率为55.4%。单因素分析结果显示,初诊骨髓原始细胞比例≥50%(P=0.015)、合并TP53突变(P<0.001)、未达到CR/CRi状态(P<0.001)是影响患者OS的不良预后因素,且多因素分析显示,上述危险因素均是影响患者OS的独立危险因素(均P<0.05)。所有患者均发生Ⅲ~Ⅳ级血液学不良反应,主要出现在第1个疗程。非血液学不良反应主要为肺部感染,患者基本可以耐受,仅1例患者因合并严重肺部感染于早期死亡。结论:维奈克拉联合阿扎胞苷方案治疗老年初治AML患者安全有效。患者年龄、初诊血红蛋白、ASXL1突变及TP53突变是患者疗效的预测因素,初诊骨髓原始细胞比例、TP53突变及是否达CR/CRi状态是影响患者生存的独立危险因素。

Objective:To investigate the efficacy and safety of venetoclax combined with azacitidine in elderly patients with newly diagnosed acute myeloid leukemia(AML).Methods:The clinical data of 27 elderly patients with newly diagnosed AML who received venetoclax combined with azacitidine in The Second Affiliated Hospital of Air Force Military Medical University from September 2020 to December 2021,were retrospectively analyzed.The incidence of complete remission(CR)/CR with incomplete hematological recovery(CRi)rate,overall response rate(ORR),and minimal residual disease(MRD)status were monitored,and the factors of efficacy and prognosis and safety of the treatment protocol were analyzed.Results:The median number of treatment cycles administered was 3(range,1-9),CR/CRi rate was 51.9%(14/27),and ORR was 63.0%(17/27).After the initial treatment cycle,44.4%of the patients achieved CR/CRi.Among all 14 patients with CR/CRi patients,9(64.3%)patients achieved MRD negativity after one or two treatment cycles.The response rate was higher in patients aged≥70 years(P=0.035),hemoglobin(Hgb)count at diagnosis was≥80 g/L(P=0.028),ASXL1 mutation(P=0.015),and no TP53 mutation(P=0.039).After the median follow-up time of 10.8(0.9–29.6)months,the median OS time of all the patients was unattained,and 1-year OS rate was 55.4%.In the univariate analysis,the proportion of bone marrow primordial cells upon diagnos is was≥50%(P=0.015),with TP53 mutation(P<0.001)and without CR/CRi(P<0.001)were associated with poor OS,and multivariate analysis showed that the risk factors were also independent prognostic factors for OS(P<0.05).All patients manifested grade 3-4 hematological adverse reactions mainly in the initial course of treatment.Nonhematological adverse reactions were mainly pulmonary infections.Most patients could tolerate the nonhematological adverse reactions,and only one patient died early due to severe pulmonary infection.Conclusions:Venetoclax combined with azacitidine regimen in elderly patients with newly diagnosed AML is safe and effective.The age,Hgb count at diagnosis,ASXL1 mutation,and TP53 mutation are predictive factors for the response,and the proportion of bone marrow primordial cells upon diagnosis,TP53 mutation,and CR/CRi status are independent prognostic factors for OS.