The Efficacy And Side Effects Of PI3K Inhibitor In The Treatment Of Relapsed/refractory Chronic Lymphocytic Leukemia:a Meta Analysis

Objective:This meta-analysis was did to evaluate the Clinical efficacy and safety of Phosphatidylinositol 3-kinase inhibitors in the application of relapsed/refractory chronic lymphocytic leukemia and provide reliable foundation for clinical treatment.Methods:Searching literature from Pub Med,Embase,Cochrane Library database from the building time to December,2020,in order to gain all clinical researchs about treatment of PI3K inhibitors-containing regimens on relapsed/refractory chronic lymphocytic leukemia.Making assessment for included literatures.And observation indexes was extrated from included literatures to make meta analysis by Rev Man5.3 software.The observational index were progression free survival,overall response rate,overall survival,complete response rate and most common adverse events ≥3 grades.Results:There are five literatures were involved totally.There are 4 eligible articles of Idelalisib,1 eligible articles of Duvelisib.The results are shown below:(1)Compared with control group,PI3K inhibitor-containing regimens extend progression free survival for relapsed/refractory ones[HR=0.27,95%CI(0.19-0.39)].Compared with control group,overall response rate is higher in PI3K inhibitor-containing regimens than control group for relapsed/refractory ones[75%vs 36%,RR=7.34,95%CI(2.82,19.13)].Compared with control group,PI3K inhibitor-containing regimens extend progression free survival for relapsed/refractory ones with del(17p)[HR=0.33,95%CI(0.21-0.52)].(2)Compared with control group,Idelalisib-containing regimens extend progression free survival for relapsed ones[HR=0.26,95%CI(0.18-0.37)].Compared with control group,Idelalisib-containing regimens extend overall survival for relapsed/refractory ones[HR=0.58,95%CI(0.46-0.73)].Compared with control group,overall response rate is higher in Idelalisib-containing regimensthan control group for relapsed/refractory ones[75% vs 32%,RR=9.50,95%CI(2.37,38.1)].Compared with control group,Idelalisib-containing regimens extend overall survival[HR=0.55,95%CI(0.42-0.73),P<0.05] and progression free survival[HR=0.29,95%CI(0.15-0.17)] for patients with del(17p).(3)The rate of grade ≥3 neutropenia is higher in PI3K-containing regimens than control group for relapsed/refractory ones[37% vs 25%,RR=1.62,95%CI(1.17,2.23)].The rate of grade ≥3 neutropenia is higher in Idelalisib-containing regimens for relapsed/refractory ones[39% vs 29%,RR=1.63,95%CI(1.02,2.60)].The rate of grade ≥3 pneumonia is higher in PI3K inhibitor-containing regimens than control group for relapsed/refractory ones[7% vs 1%,RR=6.11,95%CI(2.16,17.26)].The rate of grade ≥3 diarrhea is higher in PI3K inhibitor-containing regimens than control group for relapsed patients[14% vs 1%,RR=15.66,95%CI(5.22,46.96)].The rate of grade ≥3 transaminase elevation is higher in PI3K inhibitor-containing regimens than control group for relapsed/refractory ones[15% vs 2%,RR=8.47,95%CI(4.06,17.66),P<0.05].(4)The difference of complete response rate,grade ≥3 anemia are insignificant between PI3K inhibitor-containing regimens and control group for relapsed/refractory ones.The difference of grade ≥3 anemia is insignificant between Idelalisib-containing regimens and control group for relapsed/refractory ones.Conclusion:(1)In comparation with the matched group,PI3K-containing regimens extend progression free survival,improve OR rate of relapsed/refractory ones and extend progression free survival of relapsed/refractory ones with del(17p).In comparation with the matched group,Idelalisib-containing regimens extend progression free survival,overall survival,improve OR rate of relapsed/refractory ones and extend progression free survival of relapsed/refractory ones with del(17p).(2)In comparation with the matched group,PI3K inhibitor-containing regimens heightens the risk of grade ≥3 neutropenia,pneumonia and transaminase elevation.Idelalisib-containing regimens increases the risk of grade ≥3 neutropenia.(3)There’re insignificant difference in complete response,grade ≥3 anemia betwee PI3K inhibitor-containing regimens and the matched group.(4)More multicenter,international,randomised trails are needed to be carried out to support conclusions above.