Efficacy and safety of venetoclax-based combination therapy for previously untreated acute myeloid leukemia: a meta-analysis
Hongbo He, Xiaojia Wen, Huyong Zheng
Abstract
Purpose: To explore the efficacy and safety of venetoclax-based combination therapy for older patients with newly diagnosed acute myeloid leukemia (AML).Methods: We performed a systematic review and meta-analysis of clinical trials comparing venetoclax plus hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) with mono-HMAs or LDAC.The random or fixed effects model was applied to the studies based on heterogeneity.Dichotomous data were summarized using the risk ratio (RR) and 95% confidence interval (CI).Continuous variable data were reported as weighted mean differences (WMDs).Results: Nine studies, including a total of 1232 patients, were included in this meta-analysis.Thec complete remission (CR)/complete remission with incomplete hematological recovery (CRi) rate of the venetoclax (Ven) + azacytidine (Aza) group was significantly greater than that of the Aza monotherapy group (RR: 2.42; 95% CI: 1.85-3.15;P < 0.001).Similarly, the CR/CRi rate of the Ven + LDAC group was also significantly greater than that of the LDAC monotherapy group (RR: 2.57; 95% CI: 1.58-4.17;P = 0.00).The same results were observed for OS among these groups.However, the incidence of febrile neutropenia was greater in the Ven + Aza group than in the Ven + Decitabine (Dec) or monotherapy Aza group (RR: 0.69; 95% CI: 0.53-0.90;P = 0.006 and RR: 2.19; 95% CI: 1.58-3.03;P < 0.001, respectively).In addition, the Ven + LDAC group had significantly greater rates of constipation, diarrhea, nausea, and vomiting than the LDAC monotherapy group, with RRs and CIs of 0.61 (95% CI 0.44-0.83,P = 0.002), 1.81 (95% CI 1.22-2.67,P = 0.003), 1.39 (95% CI 1.06-1.82,P = 0.016), and 1.80 (95% CI 1.19-2.72,P = 0.005), respectively.Conclusion: Venetoclax combined with azacitidine, decitabine, or LDAC significantly improved the CR/CRi and OS of patients with previously untreated AML.However, venetoclax plus azacitidine or LDAC was more likely to lead to increased febrile neutropenia and gastrointestinal toxicity.