Bo Zhang1, Qiong Wu1, You Lang Zhou2, Xinyu Guo1, Jun Ge1, Jiaji Fu1. 1. Medical School of Nantong University, 19 Qixiu Road, Nantong 260001, Jiangsu, PR China. 2. The Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, PR China. Electronic address: zhouyoulang@ntu.edu.cn.
Abstract
BACKGROUND: Although available evidence from clinical trials has shown that immune checkpoint inhibitors (ICIs) combination therapy can lead to a series of immune-related adverse events (irAEs), the overall risk of irAEs on combination therapy has yet not been systematically reported. Therefore, we performed a meta-analysis to comprehensively explore the overall risks for irAEs on combination immunotherapy. METHODS: PubMed, Embase, and Google Scholar were systematically searched for relevant randomized controlled trials (RCTs) comparing combination immunotherapy to monotherapy. The meta-analysis was conducted by using Review Manager 5.3. RESULTS: A total of 11 RCTs involving 5307 patients were eligible for this meta-analysis. The risk ratio for all-grade diarrhea and all-grade colitis for combination therapy was 1.95 (95% CI 1.54, 2.46; P < 0.00001) and 4.45 (95% CI 3.04, 6.51; P < 0.00001), respectively. The risk ratio for all-grade hyperthyroidism and all-grade hypothyroidism for combination therapy was 2.84 (95% CI 1.71, 4.72; P < 0.0001) and 1.71 (95% CI 1.38, 2.13; P < 0.00001), respectively. The risk ratio for all-grade increased AST and all-grade increased ALT was 3.87 (95% CI 2.74, 5.47; P < 0.00001) and 4.29 (95% CI 3.05, 6.04; P < 0.00001), respectively. The risk ratio for all-grade hypophysitis and all-grade pneumonitis was 4.24 (95% CI 2.26, 7.98; P < 0.00001) and 2.92 (95% CI 1.60, 5.33; P = 0.0005), respectively. CONCLUSIONS: Patients receiving combination immunotherapy are at increased risk of selected all-grade irAEs. Although fatal high-grade irAEs is rare, AEs caused by combination immunotherapy should be recognized promptly in order to avoid more serious complications.
BACKGROUND: Although available evidence from clinical trials has shown that immune checkpoint inhibitors (ICIs) combination therapy can lead to a series of immune-related adverse events (irAEs), the overall risk of irAEs on combination therapy has yet not been systematically reported. Therefore, we performed a meta-analysis to comprehensively explore the overall risks for irAEs on combination immunotherapy. METHODS: PubMed, Embase, and Google Scholar were systematically searched for relevant randomized controlled trials (RCTs) comparing combination immunotherapy to monotherapy. The meta-analysis was conducted by using Review Manager 5.3. RESULTS: A total of 11 RCTs involving 5307 patients were eligible for this meta-analysis. The risk ratio for all-grade diarrhea and all-grade colitis for combination therapy was 1.95 (95% CI 1.54, 2.46; P < 0.00001) and 4.45 (95% CI 3.04, 6.51; P < 0.00001), respectively. The risk ratio for all-grade hyperthyroidism and all-grade hypothyroidism for combination therapy was 2.84 (95% CI 1.71, 4.72; P < 0.0001) and 1.71 (95% CI 1.38, 2.13; P < 0.00001), respectively. The risk ratio for all-grade increased AST and all-grade increased ALT was 3.87 (95% CI 2.74, 5.47; P < 0.00001) and 4.29 (95% CI 3.05, 6.04; P < 0.00001), respectively. The risk ratio for all-grade hypophysitis and all-grade pneumonitis was 4.24 (95% CI 2.26, 7.98; P < 0.00001) and 2.92 (95% CI 1.60, 5.33; P = 0.0005), respectively. CONCLUSIONS:Patients receiving combination immunotherapy are at increased risk of selected all-grade irAEs. Although fatal high-grade irAEs is rare, AEs caused by combination immunotherapy should be recognized promptly in order to avoid more serious complications.
Authors: Alexander D Sherry; Michael Bezzerides; Mohamed H Khattab; Guozhen Luo; Kristin K Ancell; Austin N Kirschner Journal: Strahlenther Onkol Date: 2020-01-31 Impact factor: 3.621
Authors: Santiago Correa; Abigail K Grosskopf; Hector Lopez Hernandez; Doreen Chan; Anthony C Yu; Lyndsay M Stapleton; Eric A Appel Journal: Chem Rev Date: 2021-05-03 Impact factor: 60.622