Meta-analysis Of The Efficacy And Safety Of Immune Checkpoint Inhibitors Combined With Hypomethylating Agents In The Treatment Of Acute Myeloid Leukemia And Myelodysplastic Syndromes

Objective: Systematic review of the effectiveness and safety of immune checkpoint inhibitors(ICI)combined with hypomethylating agents(HMA)in the treatment of acute myeloid leukemia(AML)and myelodysplastic syndromes(MDS).Methods: Use China National Knowledge Network,Wanfang database,Pub Med,Embase,Cochrane,American Society of Hematology and other databases for computer search to collect clinical information on immune checkpoint inhibitors(ICIs)combined with hypomethylating agents(HMA)in the treatment of AML and MDS.The research literature contains one ICIs combined with HMA and two ICIs combined with HMA treatment options.The literature search time is set to build the database to January 2021.The standard deviation and 95% confidence interval were obtained using CAL.Stata 12.0 software was used for data merging,sensitivity analysis and publication bias evaluation of the above studies.Results: Through literature screening,a total of 9 single-armed studies were included.Including 228 patients with newly diagnosed or relapsed and refractory AML and MDS.Nine studies all involved the effectiveness of ICIs combined with HMA,and four involved the adverse effects of the protocol.Meta-analysis results show that ICIs combined with HMA are effective in the treatment of AML and MDS.In terms of evaluation efficiency,the ORR was52%(95%CI: 37%∽66%),and the CR rate was 26%(95%CI: 18%∽34%,).Subgroup analysis showed that the ORR of ICIs combined with HMA in the treatment of newly diagnosed AML group was 66%(95%CI: 35%∽97%),CR rate was 55%(95%CI: 22%∽88%),The ORR of the relapsed and refractory AML group was 29%(95%CI: 20%∽37%),and the CR rate was 21%(95%CI: 13%∽29%).The ORR of ICIs combined with HMA in the newly diagnosed MDS group was 73%(95%CI: 62%∽83%),the CR rate was 33%(95%CI: 23%∽44%),and the ORR of the relapsed and refractory MDS group was 31%(95%CI: 14%∽48%),the CR rate was 10%(95%CI: 1%∽21%).In terms of safety,the incidence of grade 3 and 4 febrile neutropenia was 26%(95%CI: 4% ∽47%,I2=79.2%),and the incidence of grade 3 and 4 infection was 21%.%(95%CI: 2%∽43%,I2 = 84.9%),the incidence of grade 3 and 4rashes was 10%(95%CI: 12%∽32%,I2 =76.7%).Conclusions: This meta-analysis shows that immune checkpoint inhibitors combined with hypomethylating agents is an effective treatment plan for patients with AML/MDS,and it is effective for treating newly diagnosed AML/MDS patients.The ORR can reach 66% and 73%,respectively,even if it is used for the treatment of relapsed and refractory AML/MDS,the program has also shown considerable efficacy.And it is well tolerated and can become a new treatment option for these patients.