维奈克拉联合阿扎胞苷治疗急性髓系白血病的疗效及复发预测因素分析

Efficacy and Recurrence Factors of Veneclax Combined with Azacitidine in the Treatment of Acute Myeloid Leukemia

目的:观察急性髓系白血病(AML)患者接受维奈克拉与阿扎胞苷联合用药的疗效,探索治疗反应及复发的预测因素。方法:回顾性分析2021年1月至2022年9月在西南医科大学附属医院接受维奈克拉联合阿扎胞苷方案的30例AML患者的临床资料,观察患者的复合完全缓解(CRc)率、总体有效率(ORR)、无病生存期(DFS)。结果:治疗1个疗程后,CRc 16例,ORR为23/30。合并TP53突变的患者治疗反应差(P=0.009)。经1-2疗程后,25例患者获得CR/CRi。最终纳入24例获得CR/CRi的患者观察缓解持续时间,17例复发,复发中位时间3.9(0.6-15.9)个月。Kaplan-Meier曲线分析结果表明MRD转阴是患者维持DFS状态的有利因素(HR=0.5647,95%CI:0.2179-1.464,P=0.007),而NRAS突变是患者维持DFS的不利因素(HR=2.036,95%CI:0.6639-6.245,P=0.0003)。单因素联合多因素COX回归分析结果表明,NRAS突变是影响患者DFS的独立危险因素(HR=5.569,P<0.05)。此外,MRD转阴组(n=8)和MRD未转阴组(n=9)中出现早期复发的病例数分别为0和5例(P=0.012)。NRAS突变组(n=4)和NRAS野生型组(n=13)中出现早期复发的病例数分别为3和2例(P=0.022)。结论:TP53突变是患者接受维奈克拉联合阿扎胞苷出现较差治疗反应的预测因素。在接受上述持续性联合化疗方案下,NRAS突变是影响患者DFS的独立危险因素。此外,具有MRD未转阴及合并NRAS突变的患者发生早期复发的风险大。

Objective:To observe the efficacy of veneclax combined with azacitidine in acute myeloid leukemia(AML)patients and explore the predictors of treatment response and recurrence.Methods:The clinical data of30AML patients who received venetecla combined with azacitidine in the Affiliated Hospital of Southwest Medical University from January2021to September2022were retrospectively analyzed,composite complete remission(CRc)rate,overall response rate(ORR),and disease free survival(DFS)of patients were observed.Results:After one course of treatment,CRc was16cases and ORR was23/30.Patients with TP53 mutation had poor treatment response(P= 0.009).After1-2courses,25patients reached CR/CRi.Finally,24patients who obtained CR/CRi were included to observe the duration of remission.17patients had relapse,with a median recurrence time of3.9(0.6-15.9)months.The Kaplan-Meier curve showed that MRD negative was a favorable factor for maintaining DFS status(HR= 0.5647,95%CI:0.2179-1.464,P= 0.007),while NRAS mutation was an adverse factor for maintaining DFS(HR= 2.036,95%CI:0.6639-6.245,P= 0.0003).Univariate combined multivariate cox regression analysis showed that NRAS mutation was an independent risk factor affecting DFS in patients(HR= 5.569,P<0.05).In addition,the cases number of early recurrence in MRD negative group(n= 8)and MRD non-negative group(n= 9)was0and5,respectively,the difference was statistically significant(P= 0.012).There were3cases of early recurrence in the NRAS mutant group(n= 4)and2cases in the NRAS wild-type group(n= 13),the difference was statistically significant(P= 0.022).Conclusion:TP53 mutation is a predictor of poor response to veneclax in combination with azacitidine.With the continuation of the combination chemotherapy regimen described above,NRAS mutation is an independent risk factor for DFS in patients.Moreover,the patients with non-negative MRD and NRAS mutations are at high risk of early recurrence.