Efficacy And Safety Of Venetoclax-based Combinational Therapies In The Treatment Of Relapsed/Refractory Acute Myeloid Leukemia:a Meta-analysis

Objective:This study aimed to systematically evalute the efficacy and safety of venetoclax(VEN)-based combinational therapeutic regimens in the treatment of relapsed/refractory acute myeloid leukemia(R/R AML).Methods:We searched the databases such as CNKI,Wang Fang,VIP,CBM,Pubmed,Web of science,Embase,Cochrane of library,Science direct and clinical trials.gov to studied the related literatures on the treatment of R/R AML with VEN-based combinational regimens from the establishment of the database to November 2022.The target literature were screened strictly according to the inclusion and exclusion criteria.Methodological index for non-randomized studies(MINORS)was used to evaluate the quality of the included studies.Two researchers screened the literature independently,extracted the required data.This meta-analysis was conducted using STATA 15.0 software.Results:This study included 22 articles and 601 cases.The meta-analysis indicated that the VEN-based combinational regimens in the treatment of R/R AML had a pooled overall response rate(ORR)of 48%(95%CI:40%-56%,I~2=71.65%,P=0.00),a pooled complete response(CR)rate of 14%(95%CI:9%-20%,I~2=69.03%,P=0.00)and a pooled CR with incomplete count recovery(CRi)rate of 13%(95%CI:7%-19%,I~2=75.96%,P=0.00).Subgroup analysis showed,there were significant differences between among VEN plus immunochemotherapy subgroup,VEN plus chemotherapy subgroup and VEN plus targeted therapy subgroup with pooled ORR of 55%(95%CI:44-67%),48%(95%CI:37-60%)and 38%(95%CI:19-60%).However,there was no statistical significance among the three subgroups(P=0.054).The ORR of patients with previous treatment line number≤2 was 50%(95%CI:40%-61%),while that of patients with previous treatment line number>2 was45%(95%CI:22%-70%).The ORR was 53%(95%CI:38%-67%)in patients under60 years old and 41%(95%CI:30%-53%)in subgroups over 60 years old.The ORR of patients who had received transplantation was 49%(95%CI:27%-74%),while the ORR was 29%(95%CI:10%-71%)of those who had not received transplantation.In addition,the median overall survival(m OS)for treatment of R/R AML with the VEN-based combinational regimen was 7.10 months(95%CI:5.67-8.52).The VEN plus chemotherapy subgroup’s m OS was 7.89 months(95%CI:5.73-10.04).The VEN plus immunochemotherapy subgroup’s m OS was 6.75 months.The VEN plus targeted therapy subgroup’s m OS was 6.08 months.However,there was no statistical significance among the three subgroups(P>0.05).The most common hematologic adverse events of VEN-based combinational regimens were thrombocytopenia,febrile neutropenia and anemia,with incidence rates of 45%,39%and 30%respectively.Conclusion:In conclusion,the meta-analysis showed that VEN-based combinational therapies are the safe and effective options for the treatment of R/R AML.