| OBJECTIVE:The aim of this study was to evaluate the benefits and risks of Venetoclax in the treatment of chronic lymphoblastic leukemia(Chronic Lymphocytic Leukemia,CLL)via meta-analysis,and to provide the theoretical basis for the choice of clinical therapy.BACKGROUND:B-cell leukemia/lymphoma 2 protein(Bcl-2)is a member of the apoptosis regulatory protein family,which is often highly expressed in CLL,non-Hodgkin’s lymphoma and myeloma.Tumor cells often take advantage of this kind of anti-apoptotic receptor pathway to escape from the clinical treatment.Venetoclax is a selective inhibitor of Bcl-2,which was approved by FDA in 2016.It has been certified to be highly effective and safe in the therapy of many kinds of malignant leukemia,including CLL.METHODS:Searching key words-"Venetoclax" and "chronic lymphocytic leukemia" from the databases,PubMed,Web of Science and ClinicalTrails.gov,to find the relevant studies which satisfy with the observation requirements.Then reading and extracting the relevant data from those literatures,and combining the overall response rate(OR),complete response rate(CR)and partial response rate(PR)to evaluate the efficacy and safety of Venetoclax treatment.RESULTS:A total of 1152 people were included in 13 articles,including 793 males and 359 females.①Compared with the efficacy of monotherapy and combinatory therapy on CLL,the ORR with monotherapy was 77%,the CRR was 16%.When considered with combinatory therapy of Venetoclax+ rituximab,Venetoclax+obinutuzumab and Venetoclax+Ibrutinib,the ORR were 86%,97%and 89%,the CRR was 51%,55%,74%,respectively.As for triple selection of Venetoclax+lbrutinib+obinutuzumab and Bendamustine+Venetoclax+Obinutuzumab,the ORR wer 88%,95%and CRR were 39%and 40%,separately.②According to the disease status of CLL patients,comparing the treatment-naive and relapsed/refractory patients treated with Venetoclax,the ORR,CRR and PRR of treatmentnaive patients were 84%,54%and 41%,and the ORR,CRR and PRR of relapsed/refractory CLL patients were 82%,34%and 48%,respectively.③Neutropenia was the most common adverse effect(AE)in all grades of adverse events in CLL patients treated with Venetoclax monotherapy.The incidence of hematological events was higher in all events,mainly neutropenia(42.9%),thrombocytopenia(17.8%),anemia(17.4%),non-hematological adverse events manifested as vomiting(5%),hypokalemia Hyperemia(2%),hyperglycemia(1.16%).④Diarrhea is the most common AE in all grades of adverse events in CLL patients treated with Venetoclax combinatory therapy.The incidence of non-blood system events was higher in all events:nausea(44.9%),fatigue(42.7%),hypertension(30%),arthralgia(28.6%),upper respiratory tract infection(24.4%),headache(21.8%),while the incidence of hematological events was relatively low.⑤Bias assessments were performed on all ORR,CRR,PRR,and AEs in CLL patients treated with single or combined drugs,and there were no significant biases in all results.CONCLUSION:①Venetoclax single or combined drug showed good effect in the treatment-naive and relapsed/refractory CLL.②On the choice of the therapy determination,the efficacy of combinatory therapy was better than monotherapy,in which the OR rate of Venetoclax combined with second-generation CD20 monoclonal antibody is significantly higher;the CR rate of Venetoclax combined with ibrutinib is significantly higher.In addition,it is not recommended to add alkylating agents to the above two drug combinations③Taking AE events into account,patients’ clinical manifestations were different from each other after receiving mono-or combinatory therapies.The incidence of hematological events was higher when treated with monotherapy,while opposite in combinatory therapy.In general,the combination of Venetoclax,especially the two-drug regimen of Venetoclax combined with CD20 monoclonal antibody and Venetoclax combined with ibrutinib,has better clinical efficacy and safety. |
PDF Full Text Request