The Efficacy And Safey Of Venetoclax Combined With Hypomethylating Agents Or Low-dose Cytarabine For Patients With Untreated Acute Myeloid Leukemia Ineligible For Intensive Chemotherapy :a Meta-analysis

Objective: The aim of the study was to evaluate the efficacy and safey of Venetoclax in the treatment to patients who untreated acute myeloid leukemia(AML)ineligible for intensive chemotherapy,and to provide theoretical basis for clinical treatment of AML.Methods: The literature comes from VIP,Wanfang,Sinomed,CNKI,Web of science,Pub Med,Embase,The Cochrane Library,China Clinical Experiment Registration Center,Clinical Trials.gov et al.Search by subject word and free word.Filter out relevant literatures that meet the requirements and extract data through inclusion and exclusion criteria.The efficacy of Venetoclax combined with HMA or LDAC was evaluated by OS,CR,and CR/CRi indicators.Safety was assessed by the incidence of AEs,grade ≥3 adverse events,serious adverse events,and mortality indicators.Results:1.A total of 6 articles were included,with a total of 856 patients,including 495 males and 361 females.1.Efficacy assessment: venetoclax+ HMA/LDAC for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy,CR is 0.388,CR/CRi is 0.650.Venetoclax+HMA/LDAC treatment is not suitable for intensive chemotherapy and untreated AML,CR rate is 0.388,CR/CRi rate is 0.650.Subgroup analysis compared the curative effect of Ven+HMA group and Ven+LDAC group,the CR of Ven+HMA group was 0.449,the CR/CRi rate is 0.713,the CR of Ven+LDAC group is 0.267,and the CR/CRi rate is 0.502.(1)According to the subgroup analysis of genetic cell risk level,comparing the curative effect of middle-risk and high-risk AML patients,the CR/CRi rate is 0.728 and 0.538.(2)Analysis by age subgroup: comparing the curative effect of AML patients aged <75 years and ≥75 years old,the CR/CRi rate is 0.620 and0.607.(3)Subgroup analysis by blood disease type: comparing the efficacy of denovo and secondary AML patients,CR/CRi rate is 0.698,0.567 respectively.(4)According to the subgroup analysis of concomitant mutation,comparing the efficacy of FLT3/IDH12/NPM1/TP53 among different mutation groups,the CR/CRi rate is 0.643,0.759,0.851,0.459.According to different treatment regimens,the differences in efficacy between the two groups were compared: in the VEN+HMA group,the CR/CRi with FLT3/IDH1 2/NPM1/TP53 mutations were 0.744,0.783,0.851,and 0.561,respectively;the CR/CRi in the VEN+LDAC group rare is 0.444,0.659,0.830,and 0.211 respectively.2.Safety assessment All-grade AEs are most commonly nausea(0.551),vomiting(0.301),diarrhea(0.449),constipation(0.398),hypokalemia(0.336),fatigue(0.352),and are associated with gastrointestinal symptoms.Grade≥3 adverse events were most commonly febrile neutropenia,thrombocytopenia,neutropenia,and anemia,which are related to hematology.Low incidence of serious adverse events.venetoclax combined with hypomethylating agents or low-dose cytarabine has lower incidence of tumor lysis syndrome in AML;and lower mortality than intensive chemotherapy and low-intensity therapy.Conclusion: Venetoclax combined with HMA or LDAC regimens have good efficacy in the treatment of untreated AML patients who are not suitable for intensive chemotherapy.Venetoclax combined with HMA or LDAC is more effective than HMA or LDAC monotherapy;the remission rate of Venetoclax combined with HMA is relatively high.Common adverse reactions in the Venetoclax combination regimen are mostly related to gastrointestinal symptoms and are controllable;adverse reactions above grade 3 are related to hematology and usually require dose reduction or interruption.AML tumor lysis syndrome occurs less frequently with Venetoclax and with appropriate mitigation measures to limit pretreatment white blood cell counts or tumor burden.