Correlation Of Bcl-2 Expression With The Efficacy Of Venetoclax In Myeloid Tumors

Background and Purpose : Bcl-2 protein is highly expressed in some hematologic tumors,and most of the high Bcl-2 expression is associated with chemotherapy resistance and shorter overall survival in patients.Venetoclax(VEN)is a Bcl-2 inhibitor,and VA combination therapy(azacitidine + VEN)has shown good response in most patients with myeloid tumors.However,myeloid tumors are highly heterogeneous,and there are few reports on whether Bcl-2 expression differs in myeloid tumors and whether it correlates with prognosis or the efficacy of VEN therapy.Therefore,this study was conducted to investigate the differences in Bcl-2 expression in myeloid patients and its correlation with the efficacy of VEN,in order to provide a reference for the scientific and rational use of clinical drugs.Methods: Subjects: 214 patients with myeloid tumors who attended the Sichuan Provincial People’s Hospital from July 2018 to December 2022.METHODS: Bcl-2protein expression of patients was detected by immunohistochemical staining technique.DIVISION: Patients were divided into Bcl-2 negative and positive groups according to Bcl-2 expression.Statistical Methods: The chi-square test was used to compare the count data between groups,the Log-Rank test was used to compare the survival between groups,and the Cox regression model was used for univariate and multifactorial analysis.Chemotherapy regimen: VEN 400 mg/d orally,if combined with azole antifungal drugs,VEN was reduced to 100-200 mg/d.Efficacy assessment:patients with AML were assessed according to the 2017 ELN efficacy determination criteria,and patients with MDS were assessed according to the efficacy criteria proposed by the International Working Group.Results: The 63.6%(91/143)of AML patients and the 53.5%(38/71)of MDS patients were positive for Bcl-2 protein,and only the 15%(3/20)of normal controls were positive.Among patients with primary AML,the 27.1%(13/48)of patients ≥60years of age were negative for Bcl-2 protein and the 72.9%(35/48)were positive;the13.5%(7/52)Bcl-2-positive group was associated with ASXL1 gene mutation.The57.9%(11/19)of MDS patients in the BCL-2-negative group and the 28.1%(9/32)of patients in the positive group fusion gene was negative;and the 18.6%(4/22)Bcl-2-positive patients were accompanied by NPM1 mutation.After initial induction of the VA regimen in patients with primary AML,the overall CR/CRi rate was 73.3%,with73.9% and 73.0% in the Bcl-2 negative and positive groups,respectively;adverse effects were mainly hematological,with grade IV thrombocytopenia in 38.4% of the negative and 10.8% of the positive group;m OS was 14.27 months,with 14.13 months in the negative group and the total CR/m CR rate was 71.4% in MDS patients,66.7%and 75.0% in the Bcl-2 negative and positive groups,respectively;adverse events remained hematologic adverse reactions;m OS was 6.87 months,2.93 months in the negative group,and 7.47 months in the positive group.Conclusions: Bcl-2 protein is highly expressed in patients with myeloid tumors and is a factor in poor patient prognosis.In AML patients,VA regimens are efficient and reliable,and Bcl-2-positive elderly patients with poor molecular genetics benefit significantly from VA regimens.In high-risk MDS patients,VA regimens are also safe and effective,especially in Bcl-2-positive elderly patients with very high-risk IPSS-R patients,with higher remission rates and longer overall survival.