The Efficacy And Safety Of Ibrutinib Monotherapy In Patients With Chronic Lymphocytic Leukemia:a Systematic Evaluation

Objective:To evaluate the efficacy and safety of ibrutinib monotherapy on the treatment of chronic lymphocytic leukemia.Methods:A literature retrieval was conducted in CNKI 、 Wanfang Database 、 Weipu database,Pub Med,Web of Science,Embase,Cochrane Library and other databases and evaluated the quality of the literature and extracted the data.Finally,Stata 15.1was used for statistical analysis to calculate the effective rate、incidence of adverse reactions and drug withdrawal.Results:A total of 13 English literatures were included for systematic review.The overall response rate of ibrutinib monotherapy for chronic lymphocytic leukemia was 86%(95%CI: 81%-90%),and the complete response rate was 16%(95%CI: 11%-20%).The 2-year PFS was 80%(95%CI: 71%-89%),and the 2-year OS was 86%(95%CI: 75%-98%).The overall response rate and complete response rate were 92%(95%CI:87%-96%),30%(95%CI:18%-42%),83%(95%CI:78%-88%)and 12%(95%CI:6%-17%)for the patients with initial patients and relapsed/refractory patients respectively.The 2-year PFS of initial patients was 92%(95%CI: 85%-99%),the 2-year PFS and OS of relapsed/refractory patients were 72%(95%CI: 67%-77%)and 79%(95%CI:74%-84%),respectively.Subgroup analysis of the literature showed that the overall response rate and complete response rate in clinical trial and real world were 86%(95%CI: 80%-91%),17%(95%CI: 11%-22%)and 85%(95%CI:78%-92%),6%(95%CI:-9%-21%),respectively.In terms of safety,the incidence of neutropenia,thrombocytopenia,and hemoglobinia in hematological adverse events ≥ grade3 were 18%(95%CI: 13%-22%),11%(95%CI: 5%-15%),and 10%(95%CI: 4%-14%),respectively.The incidence of infection and atrial fibrillation were 25%(95%CI: 15%-34%)and 6%(95%CI: 1%-12%)among ≥3 grade nonhematologic adverse events;The rates of drug withdrawal due to disease progression and adverse events were 19%(95%CI:12%-26%)and 16%(95%CI:10%-21%).The results of subgroup analysis were as follows: the neutropenia and thrombocytopenia of grade 3 in clinical trial and real world were 17%(11%-24%),11%(5%-17%)and 21%(-7%-48%),14%(-1%-29%),respectively;The incidence of≥3 grade infection and atrial fibrillation in clinical trials and the real world were 24%(14%-35%),7%(1%-12%)and 24%(-11%-60%),3%(-13%-18%).The rates of drug withdrawal due to disease progression and adverse events in clinical trials and the real world were 20%(12%-28%),16%(11%-22%)and 17%(2%-31%),11%(11%-22%).Conclusion:Treatment with ibrutinib monotherapy is effective in Chronic Lymphocytic Leukemia patients,it has low incidence of serious adverse events,and the overall adverse events can be tolerated.It was more effective in untreated patients than in relapsed/refractory patients.In the real world,the ORR of ibrutinib monotherapy for CLL is basically consistent with the clinical trials,but the CR rate is significantly different from that of clinical trials,which needs further study.